Multi-phase oral composition

ABSTRACT

A multi-phase oral composition for whitening teeth.

FIELD OF THE INVENTION

The present invention relates to multi-phase oral composition forwhitening teeth.

BACKGROUND OF THE INVENTION

Currently in the marketplace are dental products by which variouscosmetic and/or therapeutic actives are delivered to teeth and the oralcavity. Examples of such products include: brushing aids, such asdentifrice products for delivery of oral care actives for examplepolyphosphates or fluorides; mouthwashes containing breath fresheners orantibacterial actives; and whitening strips for the delivery ofbleaching actives to the teeth. In particular the use of a dental striphas been recognized as a convenient and inexpensive way to delivercosmetic and therapeutic benefits to the teeth and mucosal surfaces ofthe oral cavity; for example, dental whitening strips, where a whiteningcomposition is applied to a strip and thereafter applied to the teeth toachieve sustained contact between the teeth and the whiteningcomposition.

Despite the above known approaches for the treatment of oral conditions,especially for the whitening of teeth, a need still exists for providingproducts with both improved bleaching efficacy, increased speed ofwhitening, decreased tooth-sensitivity, and/or decreased oral softtissue irritation. The prior art has generally attempted to addressimproved bleaching efficacy and/or increased speed of whitening byincreasing the level of the bleaching agent in the compositions. Thisapproach, however, presents several problems. First the participant mayexperience increased irritation and/or sensitivity which may beassociated with using an increased amount of a bleaching agent.Furthermore, some regulatory authorities and legislation in variousgeographies throughout the world do not allow bleaching agents to beused in products at levels above certain concentrations. Therefore,despite the above known approaches for the treatment of oral conditions,especially for the whitening of teeth, a need still exists for providingproducts with improved bleaching efficacy, increased speed of whitening,decreased tooth-sensitivity, and/or decreased oral soft tissueirritation. The present invention overcomes some of the limitations ofthe prior art, and relates to a multi-phase oral composition comprisinga bleaching agent, an aqueous phase, and a hydrophobic phase, wherein incertain embodiments the hydrophobic phase may be in predominantproportion relative to the aqueous phase.

SUMMARY OF THE INVENTION

Without being bound to a theory it was surprisingly found that bleachingagents are effective in very low concentration, if presented in amulti-phase oral composition as disclosed herein.

A multi-phase oral composition is provided that comprises in certainembodiments, more than 0.5% to about 10% of a bleaching agent, about 0.9to about 60% an aqueous phase, and about 40% to about 99.1% of ahydrophobic phase by weight of the multi-phase oral composition; whereinthe hydrophobic phase or the multi-phase oral composition has a conepenetration consistency value from about 50 to about 400 or thehydrophobic phase has a melt point from about 30° C. to about 90° C.;wherein the hydrophobic phase may be a predominant portion of themulti-phase oral composition; and wherein in certain embodiments themulti-phase oral composition may be a water-in oil emulsion.

The present invention may be used to deliver whitening benefits to theoral cavity by directly applying the composition to the teeth. Inaddition, the composition may be applied via a delivery carrier, such asa strip or film of material, dental tray, sponge material or mixturesthereof. The delivery carrier may be attached to the teeth via thecompositions herein or the adhesion function can be provided independentof the present compositions herein (e.g. can be provided via a separateadhesive composition used with the present compositions and deliverycarrier).

The delivery carrier may be attached to the teeth via an attachmentmeans that is part of the delivery carrier, for example the deliverycarrier may optionally be of sufficient size that once applied thedelivery carrier overlaps with the oral soft tissues rendering more ofthe teeth surface available for bleaching. The delivery carrier may alsobe attached to the oral cavity by physical interference or mechanicalinter-locking between the delivery carrier and the oral surfacesincluding the teeth.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a delivery system 10 comprising a stripof material 12 having rounded corners upon which in a second layer 14the present compositions are coated.

FIG. 2 is a cross-sectional view, taken along section line 3-3 of FIG.1, showing an example of the strip.

FIG. 3 is a cross-sectional plan view, showing the delivery system 10attached to the teeth 22 by means of the second layer 14 compositionlocated between the teeth 22 and the strip of material 12.

FIG. 4 is a cross-sectional elevation view of a tooth, taken alongsection line 6-6 of FIG. 3, showing the delivery system 10 adhesivelyattached to the teeth 22.

FIG. 5 shows a dental tray 30 suitable to be used with the compositionof the present invention.

FIG. 6 shows a device for delivering electromagnetic radiation with apeak intensity wavelength of about 455 nm to a transparent mouthpiece tohelp position the electromagnetic radiation reproducibly toward thetooth surface; according to certain embodiments of the presentinvention.

FIG. 7 shows the bleaching efficacy on a natural tooth surface after 14treatments using a composition of the present invention (Example-IAdelivered on a strip and used with Electromagnetic radiation having apeak intensity wavelength of 455 nm).

FIG. 8 illustrates the aqueous phase droplets Vs. air-bubbles Vs. inkpatterns as part of the procedure to measure the two-dimensional densityof droplets of aqueous phase of a multi-phase oral composition.

FIG. 9 illustrates the procedure to smear the composition onto theperoxide test strips.

FIG. 10 illustrates a sample digital image.

FIG. 11 illustrates a sample digital image.

FIG. 12 illustrates the container and roller mixer.

FIG. 13 illustrates a sample digital image.

DETAILED DESCRIPTION OF THE INVENTION

The present invention comprises a multi-phase oral composition forwhitening teeth, which in certain embodiments comprises more than 0.5%to about 10% of a bleaching agent, about 0.9 to about 60% an aqueousphase, and about 40% to about 99.1% of a hydrophobic phase by weight ofthe multi-phase oral composition; wherein the hydrophobic phase or themulti-phase oral composition has a cone penetration consistency valuefrom about 50 to about 400 or the hydrophobic phase has a melt pointfrom about 30° C. to about 90° C.

By “oral care composition”, as used herein, is meant a product, which inthe ordinary course of usage, is not intentionally swallowed forpurposes of systemic administration of particular therapeutic agents,but is rather retained in the oral cavity for a time sufficient tocontact dental surfaces or oral tissues. Examples of oral carecompositions include dentifrice, tooth gel, subgingival gel, mouthrinse, mousse, foam, mouth spray, lozenge, chewable tablet, chewing gum,tooth whitening strips, floss and floss coatings, breath fresheningdissolvable strips, or denture care or adhesive product. The oral carecomposition may also be incorporated onto strips or films for directapplication or attachment to oral surfaces.

The term “dentifrice”, as used herein, includes tooth orsubgingival—paste, gel, or liquid formulations unless otherwisespecified. The dentifrice composition may be a single phase compositionor may be a combination of two or more separate dentifrice compositions.The dentifrice composition may be in any desired form, such as deepstriped, surface striped, multilayered, having a gel surrounding apaste, or any combination thereof. Each dentifrice composition in adentifrice comprising two or more separate dentifrice compositions maybe contained in a physically separated compartment of a dispenser anddispensed side-by-side.

The term “immiscible” as used herein means less than 1 part by weight ofthe substance dissolves in 99 parts by weight of a second substance.

The term “phase” as used herein means a physically distinct region orregions, which may be continuous or discontinuous, having one or moreproperties that are different from another phase. Non-limiting examplesof properties that may be different between phases include composition,viscosity, solubility, hydrophobicity, hydrophilicity, and miscibility.

The term “multi-phase oral composition” as used herein comprises amixture of two or more phases that are immiscible with each other, forexample such as water in oil emulsions. The phases may be continuous,discontinuous, or combinations thereof. Examples of multi-phase oralcompositions include emulsions, such as water in oil emulsions. Examplesof multi-phase oral compositions also include oil-in-water emulsions,water-in-oil-in-water emulsions, and oil-in-water-in-oil emulsions.Examples of multi-phase oral compositions also include compositionswhere the phases are multi-continuous including bi-continuous, layered,striped, marbled, ribbons, swirled, and combinations thereof.

The term “emulsion” as understood herein is an example of a multi-phaseoral composition wherein: 1) at least one of the phases is discontinuousand 2) at least one of the phases is continuous. Examples of emulsionsinclude droplets of water dispersed in oil. In this example the waterand oil would be mutually immiscible with each other, water would be thediscontinuous phase, and the oil would be the continuous phase.

The term “water-in-oil emulsion” as understood herein is an example ofan emulsion wherein 1) the discontinuous phase is aqueous, and 2) thecontinuous phase is hydrophobic.

The term “aqueous phase” as understood herein is at least one phase thatcomprises water and a bleaching agent, and is immiscible with thehydrophobic phase. In certain embodiments, each part of the aqueousphase contains at least 2% of the bleaching agent by weight of theaqueous phase. Optionally the aqueous phase may further compriseingredients that are water soluble, water miscible, or combinationsthereof, such as for example water soluble solvents, alcohol,polyethylene glycol, carbopol, etc. or mixtures thereof. In someembodiments, if and when immiscible fillers are added to the aqueousphase, the percentage of the aqueous phase in the composition iscalculated by excluding the immiscible filler.

The term “hydrophobic phase” as understood herein means all componentsof the composition that are immiscible with the aqueous phase. Incertain embodiments, the hydrophobic phase may further compriseingredients that are soluble, miscible or combinations thereof in thehydrophobic phase, such as for example hydrocarbon solvents dissolvedinto the hydrophobic phase, polyethylene dissolved into the hydrophobicphase, microcrystalline wax dissolved into the hydrophobic phase, ormixtures thereof.

The term “delivery carrier” as used herein comprises a material or anappliance that is used to hold the multi-phase oral composition againstthe tooth surface. Examples of delivery carriers include strips ordental trays

The term “strip” as used herein comprises a material 1) whose longestdimension length is generally greater than its width, and 2) whose widthis generally greater than its thickness. Strips may be rectangular,arched, curved, semi-circular, have rounded corners, have slits cut intoit, have notches cut into it, bent into three dimensional shapes, orcombinations thereof. Strips may be solid, semi-solid, textured,moldable, flexible, deformable, permanently deformable, or combinationsthereof. Strips may be made from plastic sheets including polyethylene,or wax sheets. Examples of strips include a piece of polyethylene about66 mm long, 15 mm wide and 0.0178 mm thick. Examples of permanentlydeformable strips include a piece of casting wax sheet about 66 mm long,15 mm wide, and 0.4 mm thick.

The multi-phase oral compositions herein, which may be water in oilemulsions, are useful for topical application, in particular for topicalapplication in the mouth. For example, the composition might be an oralcare composition.

As used herein, the word “or” when used as a connector of two or moreelements is meant to include the elements individually and incombination; for example X or Y, means X or Y or both.

As used herein, the articles “a” and “an” are understood to mean one ormore of the material that is claimed or described, for example, “an oralcare composition” or “a bleaching agent.”

By “safe and effective amount” as used herein means an amount of acomponent, high enough to significantly (positively) modify thecondition to be treated or to affect the desired whitening result, butlow enough to avoid serious side effects (at a reasonable benefit/riskratio), within the scope of sound medical/dental judgment. The safe andeffective amount of a component, will vary with the particular conditionbeing treated, the age and physical condition of the patient beingtreated, the severity of the condition, the duration of treatment, thenature of concurrent therapy, the specific form employed, and theparticular vehicle from which the component is applied.

By “a sufficient period of time to achieve whitening” as used herein ismeant that the composition is used or worn by the participant or theparticipant is instructed to use or wear the composition for greaterthan about 10 seconds; or greater than about 1 minute, such as fromabout 2.5 minutes to about 12 hours (for example overnight treatment),or from about 3 minutes to about 180 minutes; or greater than about 5minutes, such as from about 5 minutes to about 60 minutes; or greaterthan about 10 minutes, such as from about 10 minutes to about 60minutes; or from about 1, 5, 10, or 15 minutes to about 20, 30, 60, 120minutes per application; or any other numerical range, which is narrowerand which falls within such broader numerical range, as if such narrowernumerical ranges were all expressly written herein. In addition, thetreatments may be applied from about 1, 2, or 3 times a day to about 4,5, 6 or 7 times a day. The treatments may be applied for from about 1,2, 3, 4, 5, 6, or about 7 days to about 8, 9, 10, 11, 12, 13, 14, 21, or28 days or any other numerical range, which is narrower and which fallswithin such broader numerical range, as if such narrower numericalranges were all expressly written herein. Further, the length oftreatment to achieve the desired benefit, for example, tooth whitening,may last for a specified period of time, which may be repeated ifnecessary, for example from about one day to about six months, inparticular from about one day to about 28 days, or from about 7 to about28 days. The optimal duration and frequency of application will dependon the desired effect, the severity of any condition being treated, thehealth and age of the user and like considerations.

The term “dispenser”, as used herein, means any pump, tube, or containersuitable for dispensing oral care compositions.

By “μm” or “microns” as used herein is meant micrometer.

The term “equivalent diameter” of a droplet as used herein means thediameter of a sphere having the same volume as the droplet.

The term “two-dimensional density of droplets” as used herein means thenumber of droplets of aqueous phase a) that are present in a squarecentimeter of a two-dimensional plane in the multi-phase oralcomposition and b) wherein the cross-sectional area of the droplets inthe two-dimensional plane are larger than a specified value.

All percentages and ratios used herein after are by weight of totalcomposition (wt %), unless otherwise indicated. All percentages, ratios,and levels of ingredients referred to herein are based on the actualamount of the ingredient, and do not comprise solvents, fillers, orother materials with which the ingredient may be combined as acommercially available product, unless otherwise indicated. For example,a composition that contains 0.2857% of an aqueous solution of 35%hydrogen peroxide H₂O₂ and 99.7143% petrolatum would mean thiscomposition contains 0.2857% of an aqueous phase (the aqueous solutionof 35% H₂O₂) and 99.7143% of a hydrophobic phase (the petrolatum), and0.099995% of a bleaching agent (the H₂O₂ in the aqueous phase). Asanother example, a composition that contains 0.2857% of an aqueoussolution of 35% H₂O₂, 89.7143% petrolatum, and 10% silica dispersed inthe petrolatum would mean this composition contains 0.2857% of anaqueous phase (the aqueous solution of 35% H₂O₂), 99.7143% of ahydrophobic phase (the petrolatum and silica which are both immisciblewith the aqueous phase) including the 10% of a filler (the silica), and0.099995% of a bleaching agent (the H₂O₂ in the aqueous phase). Thiswould also mean that this composition has a ratio of the concentrationin weight percent of bleaching agent present in the aqueous phase to theconcentration in weight percent of bleaching agent present in theoverall multi-phase oral composition of 350.02 (namely 35% divided by0.099995%).

As yet another example, a multi-phase oral composition that contains0.2857% of an aqueous solution of 35% hydrogen peroxide (H2O2), 99.6143%petrolatum, and 0.1% cross-linked siloxane particles dispersed in theaqueous phase would mean this multi-phase oral composition contains0.2857% of an aqueous phase (namely the aqueous solution of 35% H2O2),99.7143% of a hydrophobic phase (namely the petrolatum and cross-linkedsiloxane particles which are both immiscible with the aqueous phase),0.099995% of a bleaching agent (namely the H2O2 in the aqueous phase),and 0.1% of a filler (namely the cross-linked siloxane particles). Thiswould mean that this composition has a ratio of the concentration inweight percent of bleaching agent present in the aqueous phase to theconcentration in weight percent of bleaching agent present in theoverall multi-phase oral composition of 350.02 (namely 35% divided by0.099995%).

All measurements referred to herein are made at about 23° C. (i.e. roomtemperature) unless otherwise specified.

“Active and other ingredients” useful herein may be categorized ordescribed herein by their cosmetic and/or therapeutic benefit or theirpostulated mode of action or function. However, it is to be understoodthat the active and other ingredients useful herein can, in someinstances, provide more than one cosmetic and/or therapeutic benefit orfunction or operate via more than one mode of action. Therefore,classifications herein are made for the sake of convenience and are notintended to limit an ingredient to the particularly stated function(s)or activities listed.

The term “teeth”, as used herein, refers to natural teeth as well asartificial teeth or dental prosthesis and is construed to comprise onetooth or multiple teeth. The term “tooth surface” as used herein, refersto natural tooth surface(s) as well as artificial tooth surface(s) ordental prosthesis surface(s) accordingly.

The term “orally acceptable carrier” comprises one or more compatiblesolid or liquid excipients or diluents which are suitable for use in theoral cavity. By “compatible,” as used herein, is meant that thecomponents of the composition are capable of being commingled withoutinteraction in a manner which would substantially reduce thecomposition's stability and/or efficacy.

Multi-Phase Oral Compositions

The multi-phase oral compositions as disclosed herein may bewater-in-oil emulsions. The multi-phase oral compositions may bemicro-emulsions or macro-emulsions.

For water-in-oil emulsions comprising a bleaching agent, it has beensurprisingly found that the size of the droplets of the aqueous phase isa factor to decrease oral/topical irritation and/or tooth-sensitivity.Without being bound by theory, if the size of the droplets of theaqueous phase is too large it may lead to large spots onoral/topical/tooth surfaces that are exposed to a high concentration ofthe bleaching agent, which in turn may lead to oral/topical irritationand/or tooth-sensitivity. In certain embodiments, the number-averageequivalent-diameter or volume-average equivalent-diameter of thedroplets of aqueous phase may be no more than about 0.001 micron, 0.01micron, 0.1 micron, 1 micron, 5 microns, 10 microns, 50 microns, 100microns, 500 microns, or 1000 microns or any other numerical range,which is narrower and which falls within such broader numerical range,as if such narrower numerical ranges were all expressly written herein.In certain embodiments, the number-average equivalent-diameter orvolume-average equivalent-diameter of the droplets of aqueous phase maybe from about 0.001 micron to about 1000 microns, preferably from about0.01 micron to about 1000 microns, more preferably from about 0.1 micronto about 100 microns, and most preferably from about 1 to about 100microns or any other numerical range, which is narrower and which fallswithin such broader numerical range, as if such narrower numericalranges were all expressly written herein. Compositions that have a highdensity of large droplets of aqueous phase may lead to oral/topicalirritation and/or tooth-sensitivity. It is worth noting that measuringthe number-average equivalent-diameter or volume-averageequivalent-diameter of the droplets of aqueous phase requires one tomeasure the entire distribution of droplets sizes in threedimensions—this may require multiple different techniques that aresuited for small, medium and large droplets. In contrast, the procedurespecified herein to measure the “two-dimensional density of droplets”can be used to measure only the large droplets and only in twodimensions—this can be done using a light microscope by counting thenumber of droplets larger than a specified size (at the two-dimensionalfocal plane), and does not require more complex equipment. In certainembodiments, the “two-dimensional density of droplets” of aqueous phasemeasured using the procedure specified herein with a cross-sectionalarea larger than about 1000, 3000, 10000, 20000, or 50000 square micronsmay be no more than about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20,25, 50, or 100 per square centimeter of the two-dimensional plane, orany other numerical range, which is narrower and which falls within suchbroader numerical range as if such narrower numerical ranges were allexpressly written herein. In certain embodiments, the “two-dimensionaldensity of droplets” of aqueous phase measured using the procedurespecified herein with a cross-sectional area larger than about 10000square microns may be no more than about 25, preferably no more than 10,more preferably no more than 5, and most preferably no more than 1 persquare centimeter of the two-dimensional plane or any other numericalrange, which is narrower and which falls within such broader numericalrange as if such narrower numerical ranges were all expressly writtenherein.

Procedure to Measure the Two-Dimensional Density of Droplets of AqueousPhase of a Multi-Phase Oral Composition

-   1. Cut one 20×20 mm grid out of an adhesive grid sticker* (supplied    by Diversified Biotech Dedham, Mass., item number GRID-1000;    purchased from VWR, Batavia, Ill., catalog number 89032-163) and    stick it to the top of a glass microscope slide (VWR Micro Slides,    Super Frost Plus, 25×75×1 mm, manufactured by VWR International,    Radnor, Pa.; purchased from VWR, Batavia, Ill., catalog number    48311-703).    -   *each grid sticker has two side-by-side 20×20 mm grids, and each        cell within each grid measures 1×1 mm-   2. Use a small spatula and place a small sample of the composition    in the middle of the adhesive grid sticker stuck to the microscope    slide. The amount of sample should be such that after it has been    pressed down per step-3, at least 100 cells of the grid are    completely covered with the composition and can be measured. Take    care to place the sample as a single blob on the adhesive grid    sticker—this helps minimize air-entrapment when the coverslip is    placed over it.-   3. Place a coverslip (VWR Microscope Cover Glasses, 22×22 mm,    purchased from VWR, Batavia, Ill., catalog number 16004-094) over    the sample-composition and press down until the sample-composition    is about 100 microns thick. This may be done by placing a second    microscope slide over the coverslip and sandwiching a pair of    coverslips as spacers on either side of the sample-composition    between the two microscope slides and manually pressing down until    the sample is about 100 microns thick. Note, to make sure each    individual sample is about 100 microns thick, the thickness of each    individual grid sticker, coverslip, and microscope slide will need    to be measured.-   4. Place the microscope slide on a microscope and focus on the    sample using light transmitted through the sample. Use a microscope    and a magnification level that a) provide a field of view    encompassing at least one whole cell of the grid such that all four    edges of the cell are visible within the field of view, and b)    enable the measurement of the cross-sectional area of droplets of    aqueous phase larger than the specified value.-   5. Center the field of view on a single cell of the grid. Count the    number of droplets of aqueous phase that: a) are visible in the cell    (including those that are on the grid lines, but taking care not to    double-count these); and b) whose cross-sectional area at the    two-dimensional focal plane is larger than the specified value. Take    care not to count residual air-bubbles (unlike droplets of aqueous    phase, air bubbles may be identified by thick dark walls in the    field of view), or features of the ink pattern on the grid sticker    (unlike droplets of aqueous phase, features of the ink pattern are    crowded together and appear only on the grid lines). FIG. 8 shows a    sample image of the droplets of aqueous phase Vs. air-bubbles Vs.    features of the ink pattern.-   6. Repeat step 5 for each cell that is completely covered by the    composition. There should at least 100 cells that are completely    covered by the composition per slide.-   7. The “two-dimensional density of droplets” with a cross-sectional    area larger than a specified value (expressed as number of droplets    per square centimeter) for this slide is calculated as: The total    number of droplets of aqueous phase whose cross-sectional area at    the two-dimensional focal plane is larger than the specified value    in all cells measured in this slide DIVIDED by the total area of all    cells measured in this slide expressed in square centimeters.-   8. Repeat steps-1-7 for a total of at least twelve slides. Average    the calculation from step-7 across all the slides measured. This is    the final “two-dimensional density of droplets” with a    cross-sectional area larger than a specified value (expressed as    number of droplets per square centimeter).

For multi-phase oral compositions that comprise peroxide, it has beensurprisingly found that the standard deviation of the peroxideconcentration of a multi-phase oral composition smeared onto peroxidetest strips is a factor to decrease oral/topical irritation and/ortooth-sensitivity during use. Each peroxide test strip has tworeaction-zones that change color (driving the RED intensity lower) inareas or spots that are contacted with peroxide. Thus, without beingbound by theory, peroxide test strips may conveniently be used as aproxy for oral/topical/tooth surfaces to identify spots of high peroxideconcentration that may lead to oral/topical irritation and/ortooth-sensitivity. Furthermore, since contact with peroxide drives theRED intensity lower in the reaction-zones, the mean RED intensity ofperoxide test strips smeared with the multi-phase oral compositionsubtracted from the mean baseline RED intensity of untreated peroxidetest strips may conveniently be used as a measure of the mean peroxideconcentration. Multi-phase oral compositions that have large spots ofhigh peroxide concentration when the multi-phase oral composition issmeared on peroxide test strips may also have large spots of highperoxide concentration when the multi-phase oral composition is appliedto oral/topical/tooth surfaces—this in turn may lead to oral/topicalirritation and/or tooth-sensitivity. In contrast, multi-phase oralcompositions that have only small spots of high peroxide concentrationwhen the multi-phase oral composition is smeared onto peroxide teststrips may also have only small spots of high peroxide concentrationwhen the multi-phase oral composition is applied to oral/topical/toothsurfaces—this in turn may lead to low oral/topical irritation and/ortooth-sensitivity. The spots of peroxide concentration when themulti-phase oral composition is smeared onto peroxide test strips can bequantified by the standard deviation of the peroxide concentration onthe test strips measured using the procedure specified herein.Multi-phase oral compositions that have large spots of high peroxideconcentration when the multi-phase oral composition is smeared ontoperoxide test strips have a high standard deviation of the peroxideconcentration on the test strips. In contrast, multi-phase oralcompositions that have only small spots of high peroxide concentrationwhen the multi-phase oral composition is smeared onto peroxide teststrips have a low standard deviation of the peroxide concentration onthe test strips.

Furthermore, multi-phase oral compositions with large droplets may causelarge spots of high peroxide concentration when the multi-phase oralcomposition is smeared onto peroxide test strips—this in turn may leadto a high standard deviation of the peroxide concentration on the teststrips. In contrast, multi-phase oral compositions that have little orno large droplets may cause only small spots of high peroxideconcentration when the multi-phase oral composition is smeared ontoperoxide test strips—this in turn may lead to a low standard deviationof the peroxide concentration on the test strips.

In certain embodiments the standard deviation of the peroxideconcentration of a multi-phase oral composition smeared onto peroxidetest strips measured using the procedure specified herein may be no morethan about 5, 10, 15, 20, 25, 30, 40, 50, or 100 or any other numericalrange, which is narrower and which falls within such broader numericalrange, as if such narrower numerical ranges were all expressly writtenherein. In certain embodiments the standard deviation of the peroxideconcentration of a multi-phase oral composition smeared onto peroxidetest strips measured using the procedure specified herein may be no morethan about 50, preferably no more than about 25, more preferably no morethan about 10, and most preferably no more than about 5, or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

For multi-phase oral compositions that comprise peroxide, it hassurprisingly been found that the mean peroxide concentration of amulti-phase oral composition smeared onto peroxide test strips is afactor to deliver bleaching efficacy. Without being bound by theory, ifthe mean peroxide concentration of a multi-phase oral compositionsmeared onto peroxide test strips is low, the mean peroxideconcentration delivered to the tooth surface during use may also be low,which could lead to low bleaching effectiveness. In contrast, if themean peroxide concentration of a multi-phase oral composition smearedonto peroxide test strips is high, the mean peroxide concentrationdelivered to the tooth surface during use may also be high, which couldlead to high bleaching effectiveness. In certain embodiments, the meanperoxide concentration of a multi-phase oral composition smeared ontoperoxide test strips measured using the procedure specified herein maybe from about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65,70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, or 225 to about 2, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95,100, 125, 150, 175, 200, or 225 or any other numerical range, which isnarrower and which falls within such broader numerical range, as if suchnarrower numerical ranges were all expressly written herein. In certainembodiments, the mean peroxide concentration of a multi-phase oralcomposition smeared onto peroxide test strips measured using theprocedure specified herein may be from about 1 to about 100, preferablyfrom about 2 to about 75, more preferably from about 5 to about 50, andmost preferably from about 10 to about 50 or any other numerical range,which is narrower and which falls within such broader numerical range,as if such narrower numerical ranges were all expressly written herein.

For multi-phase oral compositions that comprise peroxide, it hassurprisingly been found that the ratio of the mean peroxideconcentration of a multi-phase oral composition smeared onto peroxidetest strips to the standard deviation of the peroxide concentration of amulti-phase oral composition smeared onto peroxide test strips is afactor to deliver a high ratio of bleaching efficacy to oral/topicalirritation and/or tooth-sensitivity. Without being bound by theory, ifthe ratio of the mean peroxide concentration of a multi-phase oralcomposition smeared onto peroxide test strips to the standard deviationof the peroxide concentration of a multi-phase oral composition smearedonto peroxide test strips is high, the composition may deliver highefficacy combined with low oral/topical irritation and/ortooth-sensitivity during use. In contrast, if the ratio of the meanperoxide concentration of a multi-phase oral composition smeared ontoperoxide test strips to the standard deviation of the peroxideconcentration of a multi-phase oral composition smeared onto peroxidetest strips is low, the composition may deliver low efficacy combinedwith high oral/topical irritation and/or tooth-sensitivity during use.In certain embodiments the ratio of the mean peroxide concentration of amulti-phase oral composition smeared onto peroxide test strips measuredusing the procedure specified herein to the standard deviation of theperoxide concentration of a multi-phase oral composition smeared ontoperoxide test strips measured using the procedure specified herein maybe no less than about 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6,7, 8, 9, 10, 15, 20, 25, 50 or any other numerical range, which isnarrower and which falls within such broader numerical range, as if suchnarrower numerical ranges were all expressly written herein. In certainembodiments the ratio of the mean peroxide concentration of amulti-phase oral composition smeared onto peroxide test strips measuredusing the procedure specified herein to the standard deviation of theperoxide concentration of a multi-phase oral composition smeared ontoperoxide test strips measured using the procedure specified herein maybe no less than than about 0.5, preferably no less than about 1, morepreferably no less than about 2, and most preferably no less than about3.5, or any other numerical range, which is narrower and which fallswithin such broader numerical range, as if such narrower numericalranges were all expressly written herein.

Method to Measure the Mean and Standard Deviation of the PeroxideConcentration of a Multi-Phase Oral Composition Smeared Onto PeroxideTest Strips

-   1. Weigh 0.60 to 0.80 gram of the composition onto the end of a    clean hard rubber spatula (4″ long blade, from VWR, Batavia, Ill.    60510, USA., catalog number 57930-025).-   2. Take a fresh peroxide test strip (EMD Millipore Corporation,    Billerica, Mass., supplier number 1.16974.0001; purchased from VWR,    Batavia, Ill., catalog number EM1.16974.0001) out of the container,    and start a timer.-   3. Take a digital image of the peroxide test strip. The equipment    and system configuration used to take the digital image of the test    strip are specified herein. Sample digital images are shown in FIGS.    10 and 11. Place the peroxide test strip on a fresh paper towel.-   4. Hold the spatula and peroxide test strip as shown in FIG. 9.    Smear the composition (pre-weighed in step-1) with firm pressure    from left to right onto both reaction-zones on the test strip.    Repeat the smearing motion a total of three strokes from left to    right with the same sample of composition that has already been    pre-weighed onto the spatula.-   5. Move the peroxide test strip to a clean area of the paper towel.    Place a filter paper (Whatman Grade 1 Qualitative Filter Paper    Standard Grade, circle, 90 mm, supplier number 1001-090; from VWR,    Batavia, Ill. 60510, USA., catalog number 28450-081) on top of the    test strip. Apply finger pressure on top of the filter paper. Pull    the peroxide test strip out from under the filter paper (while    maintaining finger pressure on the filter paper) in a single stroke    such that excess gel is wiped off onto the filter paper and paper    towel. Make sure the reaction-zones do not get dislodged from the    peroxide test strip.-   6. Take a digital image of the peroxide test strip. The equipment    and system configuration used to take the digital image of the test    strip are specified herein. Sample digital images are shown in FIGS.    10 and 11.-   7. Steps 2 to 6 should be completed within 90 seconds on the timer.-   8. Repeat steps 1 to 7 for a total of at least eighteen peroxide    test strips.-   9. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean and standard deviation of the RED intensities of    the strip of Munsell N8 Matte Color sheet attached to the holder    that serves as a built-in Munsell N8 reference within each image.    The mean RED intensity of the built-in Munsell N8 reference within    each image should be from 204 to 212 and the standard deviation    should be no more than 3.-   10. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean and standard deviation of the RED intensities of    each reaction-zone on all peroxide test strips at BASELINE (before    smearing with the composition).-   11. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean and standard deviation of the RED intensities of    each reaction-zone on all peroxide test strips AFTER smearing with    the composition.-   12. The mean peroxide concentration of the composition smeared on    peroxide test strips is calculated as follows: First, calculate the    mean baseline RED intensity of each reaction-zone from step-10 MINUS    the mean RED intensity of the same reaction-zone after smearing with    the composition from step-11. Repeat this calculation for all    reaction-zones, and average the results across all reaction-zones on    all peroxide test strips. This is the mean peroxide concentration of    the composition smeared on peroxide test strips.-   13. The standard deviation of the peroxide concentration of the    composition smeared on peroxide test strips is calculated as:    Average the standard deviation of the RED intensities across all    reaction-zones on all peroxide test strips AFTER they have been    smeared with the composition from step-11. This is the standard    deviation of the peroxide concentration of the composition smeared    on peroxide test strips.

To validate the equipment, system configuration, and procedure specifiedherein, the mean and standard deviation of the RED intensities of aMunsell N8 Matte Color sheet (from Munsell Color, Division of X-rite,Grand Rapids, Mich., USA) needs to be measured and demonstrated to befrom 204 to 212 for the mean and no more than 3 for the standarddeviation.

Equipment to Take Digital Images of Peroxide Test Strips

-   1—Digital camera capable of capturing images at 18 million pixels    (5184×3456) resolution jpg image and capable of a shutter speed of    1/250^(th) of a second (such as Canon 60D camera from Canon USA    Inc., Lake Success, N.Y. 11042)-   1—Memory card-   1—Lens adapter if needed (such as Canon body to Nikon lens adapter)-   1—105 mm lens (such as 105 mm Micro Nikkor lens from Nikon USA Inc.    Melville, N.Y. 11747)-   1—52 mm Flash adapter ring-   1—Macro ring lite with polarization filter attached (such as Canon    MR-14EX Macro ring lite with polarization filter attached from Canon    USA Inc., Lake Success, N.Y. 11042)-   1—52 mm Rotating Circular Polarizer on the lens-   1—Tripod-   1—Sheet Munsell N8 Matte Color sheet (from Munsell Color, Division    of X-rite, Grand Rapids, Mich., USA)-   1—Holder for the peroxide test strips made using DGK Plastic Gray    card XL (from DGK Color Tools on Amazon.com) as the background, and    a strip of Munsell N8 Matte Color sheet attached to serve as a    built-in Munsell N8 reference within each image.-   1—mm scale mounted to a blank specimen strip

System Configuration to Take Digital Images of Peroxide Test Strips

-   1. The tripod is configured with the tripod mount attached to the    underside of the tripod to accommodate macro photography, with the    camera pointing down toward the table. The subject plane is 317 mm    from the sensor plane.-   2. The Nikorr 105 mm lens is attached to the Canon 60D camera body    using the Canon to Nikon adapter mount.-   3. The rotating polarizer is attached to the 105 mm Micro Nikkor    lens.-   4. The 52 mm flash adapter ring is attached to the front of the 105    mm lens.-   5. The Canon MR-14EX Macro ring lite with polarization filter is    attached to the front of the lens to the flash adapter ring.-   6. The rotating circular polarizer on the lens is rotated until the    maximum gloss/glare is removed and complete cross polarization is    achieved.-   7. The flash is set to ‘manual’ mode with the power setting set to ⅛    power.-   8. The Canon 60D camera is set to ‘manual’ mode with the ISO set to    100.-   9. The Shutter is set to 1/250^(th) of a Second.-   10. The aperture is set at f=8 on the 105 mm Micro Nikkor lens.-   11. Manual Focus is used on the 105 mm Micro Nikkor lens with the    focus to 317 mm distance from the sensor plane to the subject plane.-   12. A mounted sheet of calibrated Munsell N8 material is used to    achieve White Balance for the images.-   13. The camera is set to capture images at the 18 million pixels    (5184×3456) resolution jpg image.-   14. The total exposure setting for the camera and flash needs to be    configured such that a captured image of the Munsell N8 Matte Color    sheet has a mean RED intensity of 204 to 212 and a standard    deviation of no more than 3 measured using the procedure specified    herein.

Procedure in Adobe Photoshop CS4 to Measure the Mean and StandardDeviation of the RED Intensities

-   1. Open Adobe Photoshop CS4.-   2. On the top edge of the screen select “Window”, followed by    “Histogram”. This displays the histogram of the image. In the    Histogram window, select “Expanded view” and “Show statistics”. This    displays the histogram with statistics. Make sure the “Channel” is    set to “RED”. In Adobe Photoshop CS4, a histogram panel displays the    tonal range of an image. It shows how the pixels are distributed by    graphing the number of pixels at each of the 256 intensity levels    from 0-255 in the region of interest selected. Pixels with the same    intensity level are stacked in bars along the vertical axis. The    higher the bar the greater number of pixels at that intensity level.    The vertical bars toward the right side of the histogram indicate    pixels with higher intensities, while bars toward the left side of    the histogram indicate pixels with lower intensities.-   3. The mean and standard deviation of the RED intensities of the    Munsell N8 Matte Color sheet is measured as follows: Open a captured    image of the Munsell N8 Matte Color sheet using Adobe CS4. On the    left edge of the screen, select the “Rectangular Marquee Tool”. On    the top edge of the screen, set “Feather” to 0 px, “Style” to Fixed    size, “Width” to 5000 px, and “Height” to 3300 px. This defines a    rectangle containing 16500000 pixels whose size & shape matches the    size & shape of images of the Munsell N8 Matte Color sheet. Select    the image of the Munsell N8 Matte Color sheet using the “Rectangular    Marquee Tool”. Make sure the edges of the rectangle are within the    edges of the image of the Munsell N8 Matte Color sheet. Click the    circular symbol on the Histogram panel and make sure “Cache Level”    reads 1 in the Histogram panel. This measures and displays the mean    and standard deviation of the RED intensities the Munsell N8 Matte    Color sheet. Record these values.-   4. The mean and standard deviation of the RED intensities of the    built-in Munsell N8 reference within each image is measured as    follows: Open a captured image of the built-in Munsell N8 reference    within each image using Adobe CS4. On the left edge of the screen,    select the “Rectangular Marquee Tool”. On the top edge of the    screen, set “Feather” to 0 px, “Style” to Fixed size, “Width” to    5000 px, and “Height” to 800 px. This defines a rectangle containing    4000000 pixels whose size & shape matches the size & shape of the    built-in Munsell N8 reference within each image. Select the built-in    Munsell N8 reference within each image using the “Rectangular    Marquee Tool”. Make sure the edges of the rectangle are within the    edges of the built-in Munsell N8 reference within each image. Click    the circular symbol on the Histogram panel and make sure “Cache    Level” reads 1 in the Histogram panel. This measures and displays    the mean and standard deviation of the RED intensities of the    built-in Munsell N8 reference within each image. Record these    values.-   5. The mean and standard deviation of the RED intensities of each    reaction-zone on the peroxide test strip is measured as follows:    Open a captured image of the peroxide test strip using Adobe CS4. On    the left edge of the screen, select the “Rectangular Marquee Tool”.    On the top edge of the screen, set “Feather” to 0 px, “Style” to    Fixed size, “Width” to 1300 px, and “Height” to 1750 px. This    defines a rectangle containing 2275000 pixels whose size & shape    matches the size & shape of images of each reaction-zone on the    peroxide test strip. Select one of the two reaction-zones on the    peroxide test strip using the “Rectangular Marquee Tool”. Make sure    the edges of the rectangle are within the edges of the    reaction-zone. Click the circular symbol on the Histogram panel and    make sure “Cache Level” reads 1 in the Histogram panel. This    measures and displays the mean and standard deviation of the RED    intensities of one of the two reaction-zones on the peroxide test    strip. Record these values.

The components of the aqueous phase and hydrophobic phase are chosen toallow for the release of the bleaching agent located in the aqueousphase readily from the composition.

Without being bound by theory it is believed that when the presentinvention, which may be in the form of a water in oil emulsion, isbrought into contact with a tooth surface, the aqueous phase and thecomponents of the aqueous phase may migrate to the tooth surface. Thepossible net effect is that the teeth whitening effect is started onlyafter contact with the tooth surface to be treated. That means, thebleaching agent may be protected against environmental influence andthereby stabilized by the hydrophobic phase of the multi-phase oralcomposition until use and potentially by the hydrophobic phase in theform of a film or layer during use. Thereby, the active effect may beapplied to the tooth surface and the active agent, e.g. the bleachingagent may be potentially shielded against the oral environment duringuse. Thereby the efficacy of a whitening multi-phase oral compositionmay be enhanced and/or accelerated.

Without further being bound by theory, the present invention may improvethe delivery of the whitening agent to the tooth surface and thus thewhitening performance due to the partial hydrophobic and partialhydrophilic nature of the composition. Due to the driving forceresulting therefrom the bleaching agent present in the aqueous phase maybe driven towards the tooth surface. Thereby increased speed ofwhitening and increased efficacy of the bleaching agent may be achieved,even though surprisingly low total levels of the bleaching agent areused. The present invention, therefore, at a given total overallconcentration, such as 0.1%, 1%, or 5%, by weight or below of ableaching agent, delivers a surprisingly high level of whiteningefficacy, may require fewer applications to get the same degree ofwhitening, or may require a lower gel load (milligrams of gel per unitarea) to get the same degree of whitening.

In addition, retention of the multi-phase oral composition on the toothsurfaces may be improved as the hydrophobic phase resists salivarydilution and salivary enzymes which can decompose the peroxide. Evenfurthermore, the hydrophobic phase does not dehydrate the teeth creatingan outward flux of water created by many hydrophilic compositionscontaining hydrophilic adhesives such as polycarboxylic acid. Since thehydrophobic phase does not dehydrate the teeth it may result in asurprisingly low level of tooth sensitivity even while delivering asurprisingly high level of whitening efficacy.

In addition, the hydrophobic phase may provide further advantages. Forexample, the hydrophobic phase represents a stable matrix foringredients which are soluble in the hydrophobic phase. For example,many flavor ingredients usually used in oral compositions are soluble inthe hydrophobic phase. That means the flavor ingredients may beprotected from any influence of the active agent, for example thebleaching agent, in the oral composition. In addition, during use of theoral composition at the tooth surface at least part of the hydrophobicphase may be located—without being bound by theory—towards the soft oraltissues, such as the mucosa, thereby presenting the ingredients whichare present in the hydrophobic phase, such as flavor compounds, to theoral cavity. In addition, the hydrophobic phase may shield the activeagent, such as the bleaching agent against any influence from the oralcavity, such as dilution by saliva. The shielding effect may also applyto the tooth surface(s) themselves, wherein the hydrophobic phase mayprovide greater hydration of the teeth surfaces.

In certain embodiments, multi-phase oral compositions of the presentinvention may be in the form of a liquid, viscous liquid, gel,semi-solid, solid, particulate, powder, viscoelastic liquid,viscoelastic gel, sol, viscoelastic solid, or any combination thereof.

Aqueous Phase

The present multi-phase oral compositions comprise an aqueous phase. Incertain embodiments, the maximum amount of aqueous phase may be 0.3%,0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%,90%, or 95% by weight of the multi-phase oral composition or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein. In certain embodiments, the amount of aqueous phase maybe from about 0.9% to about 60% by weight of the multi-phase oralcomposition.

In certain embodiments, the amount of aqueous phase may be from about95%, 90%, 80%, 70%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%,10%, 5%, 4%, 3%, 2%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1%, 0.9%, 0.8%, 0.7%,0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%, 0.07%, 0.06%, 0.05%,0.04%, 0.03%, 0.02%, 0.01% or 0.002% by weight of the multi-phase oralcomposition to about 95%, 90%, 80%, 70%, 60%, 55%, 50%, 45%, 40%, 35%,30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%,1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.09%, 0.08%,0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, 0.01% or 0.002% by weight ofthe multi-phase oral composition or any other numerical range, which isnarrower and which falls within such broader numerical range, as if suchnarrower numerical ranges were all expressly written herein. In certainembodiments, the amount of aqueous phase may be from about 0.002% toabout 5%, from about 0.1% to about 2%, from about 0.1% to about 1%, orfrom about 0.1% to about 0.5% by weight of the multi-phase oralcomposition, or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein. In certain embodiments theamount of the aqueous phase may be less than about 60%, 55%, 50%, 45%,40%, 35%, 30%, 25%, 20%, 15%, 10%, 5%, 4%, 3%, 2%, 1.5%, 1.4%, 1.3%,1.2%, 1.1%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%,0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%, or 0.01% byweight of the multi-phase oral composition or any other numerical range,which is narrower and which falls within such broader numerical range,as if such narrower numerical ranges were all expressly written herein.In certain embodiments, the amount of the aqueous phase may be less thanabout 1.0% or 0.9% by weight of the multi-phase oral composition.

In certain embodiments, the aqueous phase may be from about 0.9% toabout 60%, preferably from about 6% to about 30%, more preferably fromabout 7% to about 20%, and most preferably from about 10% to about 30%by weight of the multi-phase oral composition or any other numericalrange, which is narrower and which falls within such broader numericalrange, as if such narrower numerical ranges were all expressly writtenherein.

The aqueous phase may include water, polyalkylene glycols with molecularweights from about 200 to about 20,000, humectants, and mixturesthereof. Humectants generally include edible polyhydric alcohols such asglycerin, sorbitol, xylitol, butylene glycol, polyethylene glycol, andpropylene glycol, and mixtures thereof. In certain embodiments, theaqueous phase may comprise at least about 10%, or at least about 20%water by weight of the aqueous phase.

Bleaching Agent

The present multi-phase oral compositions further comprise a safe andeffective amount of a bleaching agent, wherein the level of bleachingagent is based on the available oxygen or chlorine respectively that themolecule provides to bleach the stain. In certain embodiments, themaximum amount of bleaching agent may be 0.1%, 1%, 5%, 10%, 15%, 20%,25%, 30%, 35%, 40%, 45%, or 47.5% by weight of the multi-phase oralcomposition or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein.

In certain embodiments, the bleaching agent may be from about 0.001%,0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.095%0.099995%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%,3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or47.5% to about 0.001%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%,0.08%, 0.09%, 0.095% 0.099995%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%,0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%,25%, 30%, 35%, 40%, 45%, or 47.5% by weight of the multi-phase oralcomposition or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein.

In certain embodiments the bleaching agent level may be less than 0.09%,0.095% 0.099995%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%,1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% by weight of the multi-phaseoral composition, in some embodiments less than 0.9%, 0.8%, 0.7%, 0.6%,0.5%, 0.4%, 0.3%, 0.2%, or 0.1%, by weight of the multi-phase oralcomposition, preferably from about 0.1% to about 0.9%, more preferredfrom about 0.2% to about 0.8%, more preferred from about 0.3% to about0.7% by weight of the multi-phase oral composition or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein

In certain embodiments, the bleaching agent may be from about 0.6% toabout 10%, preferably from about 0.6% to about 6%, more preferably fromabout 1% to about 5%, and most preferably from about 1% to about 3% byweight of the multi-phase oral composition or any other numerical range,which is narrower and which falls within such broader numerical range,as if such narrower numerical ranges were all expressly written herein.

The level of bleaching agent may be based on the available oxygen orchlorine respectively that the molecule provides to bleach a stain. Incertain embodiments the bleaching agent level is less than about 0.1% byweight of the multi-phase oral composition, in certain embodiments lessthan about 0.09%, 0.08%, 0.07%, 0.06%, 0.05%, 0.04%, 0.03%, 0.02%,0.01%, or 0.001% by weight of the multi-phase oral composition, or fromabout 0.01% to about 0.099995%, from about 0.01% to about 0.095%, orfrom about 0.05% to about 0.09%by weight of the multi-phase oralcomposition, or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein. Surprisingly, the bleachingagent is significantly effective when used even at the low levels in themulti-phase oral compositions as disclosed herein, which may be in theform of water in oil emulsions.

In certain embodiments, the present multi-phase oral compositionscomprise a bleaching agent, wherein the bleaching agent may be presentin the aqueous phase from about 2%, 5%, 8.75%, 10%, 15%, 17.5%, 20%,25%, 30%, 35%,45%, 50%, 60%, or 67% to about 67%, 60%, 50%, 45%, 40%,35%, 30%, 25%, 20%, 17.5%, 15%, 10%, 8.75%, or 5%, by weight of theaqueous phase or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein.

In certain embodiments, the bleaching agent present in the aqueous phasemay be at least or more than about 17.5%, 20%, 25%, 30%, 35%,45%, 50%,or 60% by weight of the aqueous phase or any other numerical range,which is narrower and which falls within such broader numerical range,as if such narrower numerical ranges were all expressly written herein.

Ratio of Concentrations of Bleaching Agent

In certain embodiments the multi-phase oral compositions of the presentinvention deliver a high ratio of the concentration in weight percent ofbleaching agent present in the aqueous phase to the concentration inweight percent of bleaching agent present in the overall multi-phaseoral composition, as they have a high concentration in weight percent ofbleaching agent present in the aqueous phase combined with a relativelylow concentration in weight percent of bleaching agent present in theoverall multi-phase oral composition. Without being bound by theory,this surprising combination of seemingly contradictory parameters in thepresent invention delivers the bleaching agent to the tooth surface witha high driving force even when the overall concentration or amount ofbleaching agent delivered to the tooth surface is low. As a result, thehigh driving force delivers a surprisingly high level of bleachingefficacy and/or bleaching speed; while the low overall concentration orlow amount of bleaching agent delivered to the tooth surface may helpreduce tooth sensitivity

The ratio of the concentration in weight percent of bleaching agentpresent in the aqueous phase to the concentration in weight percent ofbleaching agent present in the overall multi-phase oral composition maybe from about 67000, 50000, 35000, 20000, 17500, 10000, 5000, 3500,2000, 1750, 1160, 1000, 875, 700, 580, 500, 430, 400, 380, 350, 200,175, 111, 110, 105, 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, 10, or 5 toabout 67000, 50000, 35000, 20000, 17500, 10000, 5000, 3500, 2000, 1750,1160, 1000, 875, 700, 580, 500, 430, 400, 380, 350, 200, 175, 111, 110,105, 100, 90, 80, 70, 60, 50, 40, 30, 20, 15, 10, or 5 or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

In certain embodiments, the present multi-phase oral compositionscomprises a bleaching agent, wherein the ratio of the concentration inweight percent of bleaching agent present in the aqueous phase to theconcentration in weight percent of bleaching agent present in theoverall multi-phase oral composition may be at least or more than about67000, 50000, 35000, 20000, 17500, 10000, 5000, 3500, 2000, 1750, 1160,1000, 875, 700, 580, 500, 430, 400, 380, 350, 200, 175, 110, 105, 100,90, 80, 70, 60, 50, 40, 30, 20, 15, 10, or 5 or any other numericalrange, which is narrower and which falls within such broader numericalrange, as if such narrower numerical ranges were all expressly writtenherein.

Suitable bleaching agents include agents that provide bleaching effects,stain bleaching effects, stain removal effects, stain color changeeffects or any other effect, which change, or brighten tooth color. Forexample, in certain embodiments bleaching agents comprise a source ofperoxide radicals. In addition, bleaching agents may include peroxides,metal chlorites, perborates, percarbonates, peroxyacids, persulfates,compounds that form the preceding compounds in situ, and combinationsthereof. Examples of peroxide compounds include hydrogen peroxide, ureaperoxide, calcium peroxide, carbamide peroxide, and mixtures thereof. Incertain embodiments, the bleaching agent may be hydrogen peroxide(H₂O₂). Suitable metal chlorites include calcium chlorite, bariumchlorite, magnesium chlorite, lithium chlorite, sodium chlorite,potassium chlorite, and mixtures thereof. Additional bleach agents alsoinclude hypochlorite (such as metal hypochlorite) and chlorine dioxide.Persulfates include salts of peroxymonosulfate, peroxydisulfate andmixtures thereof. The starting bleaching agent material can be anaqueous or solid material.

The bleaching agents of the present invention may be stabilized againstdegradation by the shielding effect of the hydrophobic phase. In certainembodiments, after 180 days of storage in the dark at 30° C. followingformulation, multi-phase oral compositions of the present inventioncomprised at least about 10% of the initial amount of hydrogen peroxidethey were formulated with. In certain embodiments, at least about 25% ofthe initial amount of hydrogen peroxide, at least about 50% of theinitial amount of hydrogen peroxide, or at least about 75% of theinitial amount of hydrogen peroxide may be present after 180 daysstorage of the composition at 30° C.

Optional Stabilizing Agent for the Bleaching Agent

The multi-phase oral compositions of the present invention may comprisea stabilizing agent for the bleaching agent. The bleaching agent may befurther stabilized against degradation by the multi-phase oralcomposition. Therefore, stabilizing agents may be added to the aqueousphase of the present composition. In certain embodiments, if hydrogenperoxide is used stabilizing agents may be added. Suitable stabilizingagents are for example ortho-phosphoric acid, phosphate(s), such assodium hydrogen phosphate, pyrophosphate(s), organophosphonate(s),Ethylenediaminetetraacetic acid, Ethylenediamine-N,N′-diacetic acid,Ethylenediamine-N,N′-disuccinic acid, potassium stannate, sodiumstannate, tin salts, zinc salts, salicylic acid,1-Hydroxyethylidene-1,1-diphosphonic acid, and combinations thereof. Incertain embodiments, stabilizers may be used which show additional oralcare effects, such as anti-tartar effect, produced by pyrophosphate(s)or organophosphonate(s). In certain embodiments, a stabilizing agent maybe present in a multi-phase oral composition of the present invention inan amount from about 0.0000001%, 0.000001%, or 0.00001%, to about0.00001%, 0.0001%, or 0.01% by weight of the multi-phase oralcomposition or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein. In certain embodiments, astabilizing agent may be present in a multi-phase oral composition ofthe present invention in an amount from about 0.0001%, or 0.01% to about0.01%, 0.1% or about 1% by weight of the aqueous phase or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

A stabilizing agent may also include chelants. The chelant may be acopper, iron and/or manganese chelants, or a mixture thereof. Suitablechelants may be selected from: diethylene triamine pentaacetate,diethylene triamine penta(methyl phosphonic acid), ethylenediamine-N′N′-disuccinic acid, ethylene diamine tetraacetate, ethylenediamine tetra(methylene phosphonic acid), hydroxyethane di(methylenephosphonic acid), and any combination thereof. A suitable chelant may beselected from ethylene diamine-N′N′-disuccinic acid (EDDS),hydroxyethane diphosphonic acid (HEDP) or mixtures thereof. Thestabilizer may comprise ethylene diamine-N′N′-disuccinic acid or saltthereof. The ethylene diamine-N′N′-disuccinic acid may be in S,Senantiomeric form. The stabilizer may comprise4,5-dihydroxy-m-benzenedisulfonic acid disodium salt, glutamicacid-N,N-diacetic acid (GLDA) and/or salts thereof,2-hydroxypyridine-1-oxide, Trilon P™ available from BASF, Ludwigshafen,Germany. Suitable chelants may also be calcium carbonate crystal growthinhibitors. Suitable calcium carbonate crystal growth inhibitors may beselected from the group consisting of: 1-hydroxyethanediphosphonic acid(HEDP) and salts thereof; N,N-dicarboxymethyl-2-aminopentane-1,5-dioicacid and salts thereof; 2-phosphonobutane-1,2,4-tricarboxylic acid andsalts thereof; and any combination thereof.

A stabilizer may comprise a calcium carbonate crystal growth inhibitor,such as 1-hydroxyethanediphosphonic acid (HEDP);N,N-dicarboxymethyl-2-aminopentane-1,5-dioic acid;2-phosphonobutane-1,2,4-tricarboxylic acid; and salts thereof; and anycombination thereof.

A stabilizer may comprise a hydroxamate chelant. By ‘hydroxamate’ weherein mean hydroxamic acid or a corresponding salt, for example cocohydroxamic acid (Axis House RK 853).

Hydrophobic Phase

The present invention comprises a safe and effective amount of ahydrophobic phase. In certain embodiments, the present multi-phase oralcompositions comprise a hydrophobic phase, wherein the hydrophobic phasemay be at least or more than about 5%, 10%, 15%, 20%, 25%, 30%, 35%,40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%,98%, 99%, 99.1%, or 99.5% by weight of the multi-phase oral compositionor any other numerical range, which is narrower and which falls withinsuch broader numerical range, as if such narrower numerical ranges wereall expressly written herein.

In certain embodiments, the hydrophobic phase may be at least about 95%,96%, 97%, 98%, 99%, 99.1%, or 99.5% by weight of the multi-phase oralcomposition or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein.

In certain embodiments, the hydrophobic phase may be in predominantproportion relative to the aqueous phase present in the multi-phase oralcomposition. As used herein “predominant proportion” means that thepercent by weight of the hydrophobic phase of the multi-phase oralcomposition is in excess relative to the percent by weight of theaqueous phase of the multi-phase oral composition.

The hydrophobic phase may be inert or at least partially inert. Thehydrophobic phase may interact, but in certain embodiments does notinteract or only minimally interacts with the other ingredients, such asfor example, flavors or thickeners, in the multi-phase oral composition,including the bleaching agent.

A suitable hydrophobic phase for the compositions as disclosed hereinmay have an octanol/water partition coefficient (log P_(ow)) of greaterthan about 2, 3, 4, 5, or greater than about 5.5. In certainembodiments, the hydrophobic phase shows a log P_(ow) greater than about6 or any other numerical range, which is narrower and which falls withinsuch broader numerical range, as if such narrower numerical ranges wereall expressly written herein.

Without being bound by theory, the drop melting point of the hydrophobicphase may be a factor to ensure that the composition: 1) is substantiveand does not run down the teeth or run out of the delivery carrierduring application or during use; and 2) releases an effective amount ofthe bleaching agent or active agent during use. Specifically, if thedrop melting point of the hydrophobic phase is too low, the multi-phaseoral composition may not be substantive and run down the teeth or runout of the delivery carrier during application or during use. Incontrast, if the drop melting point of the hydrophobic phase is toohigh, the multi-phase oral composition may not release an effectiveamount of the bleaching agent or active agent during use. The dropmelting point of a suitable hydrophobic phase may be in the range offrom about 40° C. to about 80° C., from about 50° to about 65° C., fromabout 50° C. to about 60° C., or any other numerical range, which isnarrower, and which falls within such broader numerical range, as ifsuch narrower numerical ranges were all expressly written herein, asmeasured according to ASTM method D127-08. In certain embodiments, thedrop melting point of the hydrophobic phase may be from about 120 C, 100C, 90 C, 85 C, 80 C, 75 C, 70 C, 60 C, 50 C, 40 C, or 30 C, to about 100C, 90 C, 85 C, 80 C, 75 C, 70 C, 60 C, 50 C, 40 C, 30 C, or 25 C, or anyother numerical range, which is narrower, and which falls within suchbroader numerical range, as if such narrower numerical ranges were allexpressly written herein, as measured according to ASTM method D127-08.

Without being bound by theory, the cone penetration consistency value ofthe hydrophobic phase or the multi-phase oral composition may be afactor to ensure that the multi-phase oral composition: 1) issubstantive and does not run down the teeth or run out of the deliverycarrier during application or during use; and 2) releases an effectiveamount of the bleaching agent or active agent during use. Specifically,if the cone penetration consistency value of the hydrophobic phase orthe multi-phase oral composition is too high, the multi-phase oralcomposition may not be substantive and run down the teeth or run out ofthe delivery carrier during application or during use. In contrast, ifthe cone penetration consistency value of the hydrophobic phase or themulti-phase oral composition is too low, the multi-phase oralcomposition may not release an effective amount of the bleaching agentor active agent during use. In certain embodiments, the cone penetrationconsistency value of the hydrophobic phase or multi-phase oralcompositions may be in the range of from about 100 to about 300,preferably in the range from about 150 to about 250, and more preferablyin the range of from about 170 to about 200 or any other numericalrange, which is narrower and which falls within such broader numericalrange, as if such narrower numerical ranges were all expressly writtenherein, as measured according to ASTM method D937-07. In certainembodiments, the cone penetration consistency value of the hydrophobicphase or multi-phase oral composition may be from about 10, 25, 50, 100,110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240,250, 300, 400, or 500, to about 25, 50, 100, 110, 120, 130, 140, 150,160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 300, 400, or 500, orany other numerical range, which is narrower, and which falls withinsuch broader numerical range, as if such narrower numerical ranges wereall expressly written herein as measured according to ASTM methodD937-07.

Without being bound by theory, for multi-phase oral compositions thatcomprise peroxide, the mean residual peroxide concentration of themulti-phase oral composition smeared on teeth may be a factor to ensurethat the multi-phase oral composition: 1) is substantive and does notwash away during use; and 2) still releases an effective amount of thebleaching agent during use. Specifically, if the mean residual peroxideconcentration of the multi-phase oral composition on a tooth surface istoo low, the multi-phase oral composition may not be substantive andwash away during use, or not release an effective amount of thebleaching agent during use. In certain embodiments, the mean residualperoxide concentration of a multi-phase oral composition smeared onteeth measured using the procedure specified herein may be from about 1,2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85,90, 95, 100, 125, 150, 175, 200, or 225 to about 2, 5, 10, 15, 20, 25,30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150,175, 200, or 225 or any other numerical range, which is narrower andwhich falls within such broader numerical range, as if such narrowernumerical ranges were all expressly written herein. In certainembodiments, the mean residual peroxide concentration of a multi-phaseoral composition smeared on teeth measured using the procedure specifiedherein may be from about 1 to about 200, preferably from about 10 toabout 200, more preferably from about 50 to about 200, and mostpreferably from about 100 to about 200, or any other numerical range,which is narrower and which falls within such broader numerical range,as if such narrower numerical ranges were all expressly written herein.

Procedure to Measure the Mean Residual Peroxide Concentration of aComposition Smeared on Teeth

-   1. Cut a circular disc (7.5 to 7.8 mm diameter×1.2 to 1.3 mm    thickness) out of the front surface of a human incisor tooth. Leave    the front surface intact but flatten the back surface that has been    cut out of tooth using sand paper. Soak the tooth-disc in 15 to 20    ml of water that meets USP specification in a glass vial for at    least 24 hours. Take the tooth-disc out of the water and place it on    a fresh paper towel with the front surface facing upward.-   2. Weigh 290 to 310 grams of water that meets USP specifications    into a cylindrical plastic container with a screw-top lid 82 to 107    mm in diameter×106 to 108 mm height (“Max 200 Long Cup Translucent”,    item number 501 220t from Flacktek, Landrum, S.C.). Pre-heat the    water in the container with the lid screwed on tight in a convection    oven with air temperature at 33 C to 35 C for at least 12 hours.-   3. Weigh 0.04 to 0.06 gram of the composition onto the tip of a    disposable lip gloss applicator (“Flocked Doe Foot Lip Gloss    Applicator” made of Nylon and Polystyrene, purchased from Qosmedix    Inc., Ronkonkoma, N.Y., catalog number 74111).-   4. Smear the composition onto the front surface of the wet    tooth-disc by first rolling the tip of the lip gloss applicator    loaded with the composition on the front surface of the tooth-disc    to transfer the composition onto the tooth-disc and then fanning out    toward the circular edge.-   5. Pick up the tooth-disc with a tweezer. Make sure the tweezer    touches only the circular edge of the tooth-disc and not the surface    of the tooth-disc smeared with the composition. Tilt the plastic    container and gently place the tooth-disc in the water on the    cylindrical wall of the container where the cylindrical wall and    flat bottom meet. Make sure the treated surface of the tooth-disc is    facing upward away from the cylindrical wall of the container.-   6. Place the cylindrical container on a roller mixer (model number    TSRT9 by Techne purchased from from VWR, Batavia, Ill., catalog    number 89132-186; or item number 04750-30 from Cole-Parmer Inc.,    Vernon Hills, Ill.). Turn on the roller mixer—this gently rotates    the container at 12 to 14 RPM. The tooth-disc should continue to    remain immersed in the water and the treated surface should continue    to face away from the rotating cylindrical wall. This rotating    motion causes the water to flow gently over the tooth-disc similar    to the gentle movement of saliva and other liquids over teeth in the    mouth. This is illustrated in FIG. 12.-   7. After 58 to 62 minutes shut off the roller mixer, take a fresh    peroxide test strip (supplied by EMD Millipore Corporation,    Billerica, Mass., supplier number 1.16974.0001; purchased from VWR,    Batavia, Ill., catalog number EM1.16974.0001) out of the container,    and start a timer.-   8. Take a digital image of the peroxide test strip. The equipment    and system configuration used to take the digital image of the test    strip are specified herein. A sample digital image is shown in FIG.    13.-   9. Remove the tooth-disc from the water using a tweezer. As before,    make sure the tweezer touches only the circular edge of the    tooth-disc and not the surface of the tooth-disc smeared with the    composition. Place the tooth-disc on a gloved finger-tip. Make sure    the surface of the tooth-disc smeared with the composition is facing    upward away from the gloved finger-tip.-   10. Place the peroxide test strip against the tooth-disc such that    one of the reaction-zones contacts the surface of the tooth-disc    with the residual composition. Pinch the peroxide test strip against    the tooth-disc between thumb and forefinger and apply firm finger    pressure between thumb and forefinger for 2 to 3 seconds.-   11. Move the peroxide test strip to a clean area of a paper towel.    Place a filter paper (Whatman Grade 1 Qualitative Filter Paper    Standard Grade, circle, 90 mm, supplier number 1001-090; purchased    from VWR, Batavia, Ill., catalog number 28450-081) on top of the    test strip. Apply finger pressure on top of the filter paper. Pull    the peroxide test strip out from under the filter paper (while    maintaining finger pressure on the filter paper) in a single stroke    such that excess gel is wiped off onto the filter paper and paper    towel. Make sure the reaction-zones do not get dislodged from the    peroxide test strip.-   12. Take a digital image of the peroxide test strip. The equipment    and system configuration used to take the digital image of the test    strip are specified herein. A sample digital image is shown in FIG.    13.-   13. Steps 7 to 12 must be completed within 3 minutes on the timer.-   14. Repeat steps 1 to 13 for a minimum of twelve teeth.-   15. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean and standard deviation of the RED intensities of    the strip of Munsell N8 Matte Color sheet attached to the holder    that serves as a built-in Munsell N8 reference within each image.    The mean RED intensity of the built-in Munsell N8 reference within    each image should be from 204 to 212 and the standard deviation    should be no more than 3.-   16. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean of the RED intensities of the reaction-zone on all    peroxide test strips at BASELINE (before pressing against the    tooth-disc).-   17. Use Adobe Photoshop CS4 with the procedure specified herein to    measure the mean of the RED intensities of same the reaction-zone on    all peroxide test strips AFTER pressing against the tooth-disc.-   18. The mean residual peroxide concentration of a composition    smeared on teeth is calculated as follows: First, calculate the mean    baseline RED intensity of each reaction-zone from step-16 MINUS the    mean RED intensity of the same reaction-zone after pressing with the    residual composition on the tooth-disc from step-17. Repeat this    calculation for all reaction-zones pressed against the tooth-disc,    and average the results. This is the mean residual peroxide    concentration of a composition smeared on teeth.

In certain embodiments, the density of the hydrophobic phase used in themulti-phase oral compositions of the present invention is in the rangeof from about 0.8 g/cm3 to about 1.0 g/cm3, from about 0.85 g/cm3 toabout 0.95 g/cm3, or about 0.9 g/cm3, or any other numerical range,which is narrower, and which falls within such broader numerical range,as if such narrower numerical ranges were all expressly written herein.

In certain embodiments, the hydrophobic phase may be a non-toxic oil,such as non-toxic edible oil. In certain embodiments, the hydrophobicphase may include non-toxic edible oils, saturated or unsaturated fattyalcohols, aliphatic hydrocarbons, long chain triglycerides, fattyesters, and mixtures thereof. In certain embodiments, the hydrophobicphase may also comprise silicones, polysiloxanes, and mixtures thereof.In certain embodiments, the hydrophobic phase may be selected frommineral oil, in certain embodiments, petrolatum and mixtures thereof,more preferred petrolatum, e.g. white petrolatum, is used as thehydrophobic phase of the present composition. Examples of petrolatuminclude Snow White Pet-C from Calumet Specialty Products (Indianapolis,Ind.), G-2191 from Sonneborn (Parsippany, N.J.), G-2218 from Sonneborn,G-1958 from Sonneborn, G-2180 from Sonneborn, Snow White V28 EP fromSonneborn, and Snow White V30 from Sonneborn, and mixtures thereof.

In certain embodiments, the aliphatic hydrocarbons may contain fromabout 10, 12, 14, or 16 to about 16, 18, 20, 22, 24, 26, 28, 30, 36, 40carbon atoms such as decane, 2 ethyldecane, tetradecane, isotetradecane,hexadecane, eicosane, and mixtures thereof. In certain embodiments, longchain triglycerides may include vegetable oils, fish oils, animal fats,hydrogenated vegetable oils, partially hydrogenated vegetable oils,semi-synthetic triglycerides, synthetic triglycerides, and mixturesthereof. In certain embodiments, fractionated, refined or purified oilsof these types can also be used. In certain embodients, examples of longchain triglyceride-containing oils include almond oil; babassu oil;borage oil; black currant seed oil; canola oil; castor oil; coconut oil;corn oil; cottonseed oil; emu oil; evening primrose oil; flax seed oil;grapeseed oil; groundnut oil; mustard seed oil; olive oil; palm oil;palm kernel oil; peanut oil; rapeseed oil; safflower oil; sesame oil;shark liver oil; soybean oil; sunflower oil; hydrogenated castor oil;hydrogenated coconut oil; hydrogenated palm oil; hydrogenated soybeanoil; hydrogenated vegetable oil; a mixture of hydrogenated cottonseedoil and hydrogenated castor oil; partially hydrogenated soybean oil; amixture of partially hydrogenated soybean oil and partially hydrogenatedcottonseed oil; glyceryl trioleate; glyceryl trilinoleate; glyceryltrilinolenate; a Ω3-polyunsaturated fatty acid triglyceride containingoil; and mixtures thereof. The long chain triglyceride containing oilsmay be in certain embodiments selected from the group consisting of cornoil, olive oil, palm oil, peanut oil, safflower oil, sesame oil, soybeanoil, castor oil, linseed oil, rape oil, rice bran oil, coconut oil,hydrogenated castor oil; partially hydrogenated soybean oil; glyceryltrioleate; glyceryl trilinoleate; a Ω3-polyunsaturated fatty acidtriglyceride containing oil; and mixtures thereof.

In certain embodiments, saturated or unsaturated fatty alcohols may havefrom about 6 to about 20 carbon atoms, cetearyl alcohol, lauryl alcohol,and mixtures thereof. For example, Lipowax (Cetearyl Alcohol andCeteareth-20) are supplied and manufactured by Lipo Chemical.

General information on silicones including silicone fluids, gums andresins, as well as the manufacture of silicones, can be found inEncyclopedia of Polymer Science and Engineering, Volume 15, SecondEdition, pp 204-308, John Wiley & Sons Inc. 1989 and Chemistry andTechnology of Silicones, Walter Noll, Academic Press Inc, (Harcourt BrueJavanovich, Publishers, New York), 1968, pp 282-287 and 409-426.

The multi-phase oral composition as disclosed herein may compriseadditional ingredients, which can be added optionally, and which will bedescribed below in further detail.

The multi-phase oral compositions of the present invention may comprisean emulsifier. Surprisingly, in certain embodiments, a multi-phase oralcomposition, which may be in the form of an emulsion may be formed evenwhen no emulsifier is used. In certain embodiments, multi-phase oralcompositions, which may be in the form of a water in oil emulsion, maybe formed even when no emulsifier is used. Without being bound by atheory it is believed that the low amount of aqueous phase, combinedwith the rheological properties, flow properties, drop melting point,and/or cone penetration consistency of the hydrophobic phase, and/or theprocess of preparation of the composition may help to disperse theaqueous phase into the hydrophobic phase and keep it dispersed withoutthe use of an emulsifying agent. In certain embodiments, multi-phaseoral compositions may be substantially free of ingredients that maycompromise the efficacy, usage experience, concentration of actives orbleaching agents at the tooth surface over time, active or bleachingefficiency, or compatibility between ingredients, for example anemulsifier. “Substantially free of an emulsifier” as understood hereinmeans that the composition comprises less than 0.001% by weight of anemulsifier. More preferred the present whitening multi-phase oralcompositions are free of an emulsifier, i.e. do not comprise anyemulsifier.

In certain embodiments, the multi-phase oral compositions may comprisefrom about 0.001% to 30% of an emulsifier. Any emulsifier may be used aslong as the emulsifier chosen is non-toxic to a user. In certainembodiments, an emulsifier (or a combination of emulsifiers) favors theformation of a multi-phase oral emulsion. In certain embodiments, thepresent multi-phase oral compositions may comprise from 0 to about 0.1%,from about 0.1 to about 5%, from about 0.1 to about 3%, or from about0.5% to about 1.5% by weight of the multi-phase oral composition, ofemulsifier.

Classes of surfactants useful as emulsifiers include nonionic, anionic,cationic, amphoteric, synthetic emulsifying agents, and mixturesthereof. Many suitable nonionic and amphoteric surfactants are disclosedby U.S. Pat. No. 3,988,433; U.S. Pat. No. 4,051,234, and many suitablenonionic surfactants are also disclosed by U.S. Pat. No. 3,959,458.

In certain embodiments, since multi-phase oral emulsions are favoredwith more lipophilic emulsifiers, the emulsifier may have an HLB valueof from about 1 to about 10, an HLB value of from about 3 to about 8, anHLB value from about 4 to about 7, or an HLB from about 4 to about 6.Either a single emulsifier may be used or a combination of emulsifiersmay be used. In certain embodiments, the emulsifier may be a blend oftwo or more emulsifiers, such as a blend of two or more nonionicemulsifiers. In this regard an emulsifier that tends to form amulti-phase oral emulsion and an emulsifier that forms an oil in wateremulsion may be blended to achieve the requisite HLB for a multi-phaseoral emulsion. (HLB values are algebraically additive)

Other emulsifiers, also useful herein include natural emulsifyingagents, such as acacia, gelatin, lecithin and cholesterol; finelydispersed solids, such as colloidal clays, bentonite, veegum (magnesiumaluminum silicate; and synthetic emulsifying agents, such as salts offatty acids, sulfates such as sorbitan trioleate, sorbitan tristearate,sucrose distearate, propylene glycol monostearate, glycerolmonostearate, propylene glycol monolaurate, sorbitan monostearate,sorbitan monolaurate, polyoxyethylene-4-lauryl ether, sodium laurylsulfate, sulfonates such as dioctyl sosium sulfosuccinate, glycerylesters, polyoxyethylene glycol esters and ethers, diethylene glycolmonostearate, PEG 200 distearate, and sorbitan fatty acid esters, suchas sorbitan monopalmitate, and their polyoxyethylene derivatives,polyoxyethylene glycol esters such as the monostearate, Polysorbate 80(ethoxylated sorbitan monooleate) (supplied by Spectrum, etc.); andmixtures thereof.

An emulsifier may be a surfactant that is non reactive with a bleachingagent. For example, surfactants that are non-reactive with a bleachingagent have no hydroxy groups, are free of nitrogen groups and linkages,are essentially free of metals such as Zn, etc.

The emulsifier may be a non-ionic surfactant. Nonionic surfactantsinclude polyoxyethylene sorbitan fatty acid esters, such as, materialssold under the trademark Tween. The number following the‘polyoxyethylene’ part in the following section refers to the totalnumber of oxyethylene —(CH₂CH₂O)— groups found in the molecule. Thenumber following the ‘polysorbate’ part is related to the type of fattyacid associated with the polyoxyethylene sorbitan part of the molecule.Monolaurate is indicated by 20, monopalmitate is indicated by 40,monostearate by 60, and monooleate by 80. Examples of such materials arepolyoxyethylene (20) sorbitan monolaurate (Tween 20), polyoxyethylene(20) sorbitan monopalmitate (Tween 40), polyoxyethylene (20) sorbitanmonostearate (Tween 60), polyoxyethylene (4) sorbitan monostearate(Tween 61), polyoxyethylene (20) sorbitan tristearate (Tween 65),polyoxyethylene (20) sorbitan monooleate (Tween 80), polyoxyethylene (5)sorbitan monooleate (Tween 81), and polyoxyethlene (20) sorbitantrioleate (Tween 85), and mixtures thereof. Polyoxyethylene fatty acidesters are also suitable and examples include those materials sold underthe trademark Myrj such as polyoxyethylene (8) stearate (Myrj 45) andpolyoxyethylene (40) stearate (Myrj 52), and mixtures thereof. Furthernonionics include, polyoxyethylene polyoxypropylene block polymers, suchas poloxamers and Pluronics.

Another suitable class of non-ionic surfactants for optional use in thepresent invention are polyoxyethylene fatty ethers, such as, thematerials sold under the trademark Brij. Examples of such materials arepolyoxyethylene (4) lauryl ether (Brij 30), polyoxyethylene (23) laurylether (Brij 35), polyoxyethylene (2) cetyl ether (Brij 52),polyoxyethylene (10) cetyl ether (Brij 56), polyoxyethylene (20) cetylether (Brij 58), polyoxyethylene (2) stearyl ether (Brij 72),polyoxyethylene (10) stearyl ether (Brij 76), polyoxyethylene (20)stearyl ether (Brij 78), polyoxyethylne (2) oleyl ether (Brij 93),polyoxyethylene (10) oleyl ether, and polyoxyethylene (20) oleyl ether(Brij 99), and mixtures thereof.

A portion of a non-ionic surfactant may be substituted with a lipophilicsurfactant, such as, sorbitan fatty acid esters such as the materialssold under the trademark Arlacel. Suitable lipophilic surfactantsinclude sorbitan monolaurate (Arlacel 20), sorbitan monopalmitate(Arlacel 40), sorbitan monostearate (Aracel 60), sorbitan monooleate(Arlacel 80), sorbitan sesquioleate (Arlacel 83), and sorbitan trioleate(Arlacel 85), and mixtures thereof. Typically, from about 2% to about90% of the level of the nonionic surfactant may be substituted by alipophilic surfactant, or from about 25% to about 50%.

In certain embodimentsthe emulsifier may be Aerosol OT (sodium dioctylsulfosuccinate) manufactured by Cytec.

In addition, in certain embodiments, the multi-phase oral compositionsmay be also substantially free of ingredients that may compromise theefficacy, usage experience, concentration of actives or bleaching agentsat the tooth surface over time, active or bleaching efficiency, orcompatibility between ingredients, for example acids and/or alcohols. Incertain embodiments, multi-phase oral compositions may comprise lessthan 0.001%by weight of the composition, of acids and/or alcohols,preferably multi-phase oral compositions do not comprise acids and/oralcohols. Without being bound by a theory it is believed that thedecrease in surface tension produced by alcohol may decrease theretention time of the aqueous phase at the tooth surface, therebydecreasing the efficacy of the oral care actives. The presence of acidsmight contradict with the actives and/or may produce negative sideeffects as the tooth surface such as hypersensitivity etc. Thus, incertain embodiments, the present multi-phase oral compositions arepreferably free of acids, free of alcohols, or free of a mixturethereof. In certain embodiments, the hydrophobic phase of themulti-phase oral composition may be substantially free of ingredientsthat may compromise the efficacy, usage experience, concentration ofactives or bleaching agent at the tooth surface over time, active orbleaching efficiency, or compatibility between ingredients, for examplebleaching agent. In certain embodiments, a multi-phase oral compositionmay be substantially free of ingredients that may compromise theefficacy, usage experience, concentration of actives or bleaching agentat the tooth surface over time, active or bleaching efficiency, orcompatibility between ingredients, for example fumed silica,polyorganosiloxanes, copolymer condensation products of silicone resinsand polydiorganosiloxanes, solid ingredients, or combinations thereof.In certain embodiments, the multi-phase oral composition may besubstantially free of fumed silica since it may decrease the stabilityof the bleaching agent, especially if the bleaching agent is in a liquidform or dissolved in a liquid.

Additional Ingredients of the Multi-Phase Oral Composition

Thickening Agents, Viscosity Modifiers, or Particulate Fillers

The multi-phase oral compositions herein may comprise a safe andeffective amount of a thickening agent, viscosity modifier orparticulate fillers. A thickening agent may further provide acceptablerheology of the composition. The viscosity modifier may further functionto inhibit settling and separation of components or control settling ina manner that facilitates re-dispersion and may control flow propertiesof the composition. In addition, a thickening agent or viscositymodifier may facilitate use of the present compositions with suitableapplications devices, such as strips, films or dental trays byincreasing the retention onto the surfaces of the application devices.The thickening agent, as described herein, may also serve as anadhesive.

When present a thickening agent, viscosity modifier, or particulatefiller may be present at a level of from about 0.01% to about 99%, fromabout 0.1% to about 50%, from about 1% to about 25%, or from about 1% toabout 10%, by weight of the multi-phase oral composition.

Suitable thickening agents, viscosity modifiers, or particulate fillersthat can be used herein include organo modified clays, silicas,synthetic polymers such as crosslinked siloxanes, cellulose derivatives(e.g. methylcellulose, carboxymethylcellulose, hydroxyethylcellulose,hydroxypropylcellulose, hydroxy-propylmethylcellulose, etc.), carbomerpolymers (e.g. crosslinked polyacrylic acid copolymer or homopolymer andcopolymers of acrylic acid cross linked with a polyalkenyl polyether),natural and synthetic gums, karaya gum, guar gum, gelatin, algin, sodiumalginate, tragacanth, chitosan, polyethylene oxide, acrylamide polymers,polyacrylic acid, polyvinyl alcohol, polyamines, polyquarternarycompounds, ethylene oxide polymers, polyvinylpyrrolidone, cationicpolyacrylamide polymers, waxes (which includes paraffin wax andmicrocrystalline waxes), polyethylene, fumed silica, polymethacrylates,olefin copolymers, hydrogenated styrene-diene copolymers, styrenepolyesters, rubber, polyvinylchloride, nylon, fluorocarbon, polyurethaneprepolymer, polyethylene, polystyrene, alkylated polystyrene,polypropylene, cellulosic resins, acrylic resins, elastomers,poly(n-butyl vinyl ether), poly(styrene-co-maleic anhydride), poly(alkylfumarate co-vinyl acetate), poly(t-butyl styrene), and mixtures thereof.

Examples of polyethylene include A-C 1702 or A-C 6702 made by HoneywellCorp. (Morristown, N.J.), with a penetration value of about 98.5 andabout 90.0, respectively, under ASTM D-1321; polyethylene Performaleneseries from Baker Hughes; this includes polyethylene Performalene 400from Baker Hughes Inc. (Houston, Tex.). Examples of microcrystalline waxinclude the Multiwax series from Sonneborn (Parsippany, N.J.), Crompton(Witco); these include Multiwax 835, Multiwax 440, Multiwax 180, andmixtures thereof.

Examples of polymethacrylates include, for example,polyacrylate-co-methacrylate, polymethacrylate-co-styrene, orcombinations thereof. Examples of elastomers include, for instance,hydrogenated styrene-co-butadiene, hydrogenated styrene-co-isoprene,ethylene-ethylene-propylene polymer, ethylene-propylene polymer,styrene-ethylene-ethylene-propylene-styrene polymer or combinationsthereof. An example of a rubber includes hydrogenated polyisoprene.Other examples of viscosity modifiers can be found in “Chemistry andTechnology of Lubricants,” Chapman and Hall (2^(nd) Ed. 1997).

Suitable carbomers comprises the class of homopolymers of acrylic acidcrosslinked with an alkyl ether of pentaerythritol or an alkyl ether ofsucrose. Carbomers are commercially available from B.F. Goodrich as theCarbopol® series, such as Carbopol 934, 940, 941, 956, and mixturesthereof. Homopolymers of polyacrylic acid are described, for example, inU.S. Pat. No. 2,798,053. Other examples of homopolymers which are usefulinclude Ultrez 10, ETD 2050, and 974P polymers, which are available fromThe B.F. Goodrich Company (Greenville, S.C.). Such polymers arehomopolymers of unsaturated, polymerizable carboxylic monomers such asacrylic acid, methacrylic acid, maleic acid, itaconic acid, maleicanhydride, and the like.

Optional Additional Oral Care Active Agents

The composition of the present invention may comprise a safe andeffective amount of an additional oral care active agent, such as anymaterial that is generally considered safe for use in the oral cavityand that provides changes to the overall appearance or health of theoral cavity. Suitable additional oral care actives include one or moreanticalculus agent(s), fluoride ion source, antimicrobial agent(s),dentinal desensitizing agent(s), anesthetic agent(s), antifungalagent(s), anti-inflammatory agent(s), selective H-2 antagonist(s),anticaries agent(s), nutrient(s), erythritol, probiotics, and mixturesthereof. The additional oral care active agent may contain an active ata level where upon directed use, the benefit sought by the wearer ispromoted without detriment to the oral surface to which it is applied.Examples of the oral conditions these actives address include, but, arenot limited to, appearance and structural changes to teeth, stainremoval, plaque removal, tartar removal, cavity prevention andtreatment, inflamed and/or bleeding gums, mucosal wounds, lesions,ulcers, aphthous ulcers, cold sores, tooth abscesses, and theelimination of mouth malodor resulting from the conditions above andother causes, such as microbial proliferation. In certain embodiments,the level of the additional oral care active that may be used in themulti-phase oral compositions may be from about 0.01% to about 50%, fromabout 0.1% to about 20%, from about 0.5% to about 10%, or from about 1%to about 7%, by weight of the multi-phase oral composition or any othernumerical range, which is narrower, and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

In certain embodiments, the additional oral care active agent may be ahealing agent that promotes or enhances the healing or regenerativeprocess. In certain embodiments, such healing agents may comprisehyaluronic acid or salts, glucosamine or salts, allantoin, curcumin, Dpanthenol, niacinamide, ellagic acid, flavanoids (including fisetin,querctin, luteolin, apigenin), vitamin E, ubiquinone, or mixturesthereof.

In certain embodiments, the additional oral care active agent may be oneor more probiotics selected from Lactobacillus reuteri ATCC 55730;Lactobacillus salivarius strain TI12711 (LS 1); Lactobacillus paracaseiADP-1; Streptococcus salivarius K12; Bifidobacterium DN-173 010;Filtrate of L. paracasei strain (pro-t-action™); S. Oralis KJ3, S.rattus JH145, S. uberis KJ2; Lactobacillus, reuteri Prodentis;Lactobacillus salivarius LS1; Lactobacillus paracasei; Lactobacillusparacasei ADP1; Streptococcus salivarius M18, K12 or BLIS K12 and BLISM18; Bacillus Amyloliquefaciens; Bacillus Clausii; Bacillus Coagulans;Bacillus Subtilis; Bacillus subtilis: E-300; Bifidobacterium Animalis;Bifidobacterium B6; Bifidobacterium Bifidum; Bifidobacterium Breve(Bb-03); Bifidobacterium DN-173 010; Bifidobacterium GBI 30 6068;Bifidobacterium infantis; Bifidobacterium Lactis; Bifidobacterium lactisBb-12; Bifidobacterium Longum; Bifidobacterium Thermophilum;Enterococcus Faecalis; Enterococcus Faecium; Enterococcus Faecium NCIMB10415; Enterococcus LAB SF 68; Lactobacilli reuteri ATCC 55730 and ATCCPTA 5289; Lactobacilli reuteri ATCC 55730 and ATCC PTA 5289 (10 : 1);Lactobacillus Acidophilus; Lactobacillus acidophilus ATCC 4356 andBifidobacterium bifidum ATCC 29521; Lactobacillus acidophilus;Bifidobacterium longum; Bifidobacterium bifidum; Bifidobacterium lactis;Lactobacillus Brevis; Lactobacillus Casei (subsp. Casi); Lactobacilluscasei Shirota; Lactobacillus Confusus; Lactobacillus crispatus YIT12319; Lactobacillus Curvatus; Lactobacillus Delbrueckii Ssp. BulgaricusPXN 39; Lactobacillus Fermentum; Lactobacillus fermentum YIT 12320;Lactobacillus Gasseri; Lactobacillus gasseri YIT 12321; LactobacillusHelveticus; Lactobacillus Johnsonii; Lactobacillus Kimchii;Lactobacillus Lactis L1A; Lactobacillus Paracasei (Lpc37); Lactobacillusparacasei GMNL-33; Lactobacillus Pentosus; Lactobacillus plantarum;Lactobacillus Plantarum; Lactobacillus Protectus; Lactobacillus Reuteri;Lactobacillus reuteri ATCC 55730; Lactobacillus reuteri SD2112(ATCC55730); Lactobacillus Rhamnosus (GG); Lactobacillus rhamnosus GG;Lactobacillus rhamnosus GG; L. rhamnosus LC705; Propionibacteriumfreudenreichii ssp; shermanii JS; Lactobacillus rhamnosus L8020;Lactobacillus rhamnosus LB21; Lactobacillus Salivarius; Lactobacillussalivarius WB21; Lactobacillus Sporogenes; Lactococcus Lactis SspDiacetylactis; Lactococcus Lactis Ssp. Lactis; Pediococcus Acidilactici;Pediococcus Pentosaceus; Saccharomyces Boulardii; SaccharomycesCerevisiae; Strep. uberis KJ2sm; Strep. oralis KJ3sm; trep. rattusJH145; Streptococcus mitis YIT 12322; Streptococcus Oralis KJ3;Streptococcus Rattus JH145; Streptococcus Salivarius (BLIS K12 or BLISM18); Streptococcus salivarius K12; Streptococcus Thermophilus;Streptococcus Uberis KJ2; Thermus thermophiles; Weissella cibaria CMS2;Weissella cibaria CMS3; and Weissella cibaria CMU.

Probiotics can be used in the multi-phase oral compositions of thepresent invention to promote positive oral health effects, such asreduce caries and plaque, promote gum health, improve breath, andpromote whitening. In certain embodiments, the efficacy of probiotics inthe multi-phase oral compositions can be determined by measuring one ormore of the following: reduction of the levels of salivary mutansstreptococci; reduction of gingival crevicular fluid; reduction ofperiodontal pathogens (C. rectus and P. gingivitis) in subgingivalplaque; decreased counts of yeast; decreased prevalence of oral candida;reduction of oral volatile sulfur compound (VSC) levels; and reductionof TNF-α and IL-8 production. Without being limited to theory it isbelieved that one or more of the above positive oral health effects maybe achieved through the production of bacterial toxins, which remove orreduce certain types of bacteria in the oral cavity; further one or moreof the above positive oral health effects may be achieved throughbacterial production of one or more enzymes that inhibit the productionof or dissolves/loosens biofilms or sticky deposits that can lead tooral health problems.

As the present multi-phase oral composition is directed to bleaching thetooth surface and removing or decreasing the stain attached thereto, incertain embodiments a safe and effective amount may be added of at leastone anticalculus agent to the compositions as disclosed herein. Incertain embodiments, said amount may be from about 0.01% to about 40%,from about 0.1% to about 25%, from about 4.5% to about 20%, or fromabout 5% to about 15%, by weight of the multi-phase oral composition orany other numerical range, which is narrower, and which falls withinsuch broader numerical range, as if such narrower numerical ranges wereall expressly written herein. The anticalculus agent may also becompatible with the other components of the multi-phase oralcomposition, in certain embodiments the whitening agent. Theanticalculus agent may be selected from the group consisting ofpolyphosphates and salts thereof; polyamino propane sulfonic acid (AMPS)and salts thereof; polyolefin sulfonates and salts thereof; polyvinylphosphates and salts thereof; polyolefin phosphates and salts thereof;diphosphonates and salts thereof; phosphonoalkane carboxylic acid andsalts thereof; polyphosphonates and salts thereof; polyvinylphosphonates and salts thereof; polyolefin phosphonates and saltsthereof; polypeptides; and mixtures thereof, wherein the mentioned saltsare usually alkali metal salts. In certain embodiments anticalculusagents used in the present multi-phase oral composition also show astabilizing effect to the bleaching agents, such as pyrophosphates,polyphosphates, polyphophonates and mixtures thereof.

For example, the anticalculus agent may be a polyphosphate. Apolyphosphate is generally understood to comprise two or more phosphatemolecules arranged primarily in a linear configuration, although somecyclic derivatives may be present. Linear polyphosphates correspond to(X PO₃)_(n) where n is about 2 to about 125, wherein preferably n isgreater than 4, and X is for example sodium, potassium, etc. For (XPO₃)_(n) when n is at least 3 the polyphosphates are glassy incharacter. Counter-ions for these phosphates may be the alkali metal,alkaline earth metal, ammonium, C₂-C₆ alkanolammonium and salt mixtures.Polyphosphates are generally employed as their wholly or partiallyneutralized water soluble alkali metal salts such as potassium, sodium,ammonium salts, and mixtures thereof. The inorganic polyphosphate saltsinclude alkali metal (e.g. sodium) tripolyphosphate, tetrapolyphosphate,dialkyl metal (e.g. disodium) diacid, trialkyl metal (e.g. trisodium)monoacid, potassium hydrogen phosphate, sodium hydrogen phosphate, andalkali metal (e.g. sodium) hexametaphosphate, and mixtures thereof.Polyphosphates larger than tetrapolyphosphate usually occur as amorphousglassy materials, such as those manufactured by FMC Corporation whichare commercially known as Sodaphos Hexaphos (n≈13), Glass H (n≈21), andmixtures thereof. If present, the present compositions will typicallycomprise from about 0.5% to about 20%, in certain embodiments from about4% to about 15%, more particular from about 6% to about 12%, by weightof the composition of polyphosphate.

The pyrophosphate salts useful in the present compositions include,alkali metal pyrophosphates, di-, tri-, and mono-potassium or sodiumpyrophosphates, dialkali metal pyrophosphate salts, tetraalkali metalpyrophosphate salts, and mixtures thereof. For example, thepyrophosphate salt is selected from the group consisting of trisodiumpyrophosphate, disodium dihydrogen pyrophosphate (Na₂H₂P₂O₇),dipotassium pyrophosphate, tetrasodium pyrophosphate (Na₄P₂O₇),tetrapotassium pyrophosphate (K₄P₂O₇), and mixtures thereof, whereintetrasodium pyrophosphate is preferred. Tetrasodium pyrophosphate may bethe anhydrous salt form or the decahydrate form, or any other speciesstable in solid form in the present compositions. The salt is in itssolid particle form, which may be its crystalline and/or amorphousstate, with the particle size of the salt preferably being small enoughto be aesthetically acceptable and readily soluble during use. The levelof pyrophosphate salt in the present compositions may be from about 1.5%to about 15%, in certain embodiments from about 2% to about 10%, andmore particular from about 3% to about 8%, by weight of the composition.

The phosphate sources, including but are not limited to, polyphosphatesand pyrophosphates, are described in more detail in Kirk & Othmer,Encyclopedia of Chemical Technology, Fourth Edition, Volume 18,Wiley-Interscience Publishers (1996), pages 685-707, incorporated hereinby reference in its entirety, including all references incorporated intoKirk & Othmer.

Polyolefin phosphonates include those wherein the olefin group contains2 or more carbon atoms. Polyvinylphosphonates includepolyvinylphosphonic acid. Diphosphonates and salts thereof includeazocycloalkane-2,2-diphosphonic acids and salts thereof, ions ofazocycloalkane-2,2-diphosphonic acids and salts thereof (such as thosewhich the alkane moiety has five, six or seven carbon atoms, in whichthe nitrogen atom is unsubstituted or carries a lower alkylsubstitutent, e.g. methyl), azacyclohexane-2,2-diphosphonic acid,azacyclopentane-2,2-diphosphonic acid,N-methyl-azacyclopentane-2,3-diphosphonic acid, EHDP(ethanehydroxy-1,1,-diphosphonic acid), AHP(azacycloheptane-2,2-diphosphonic acid, a.k.a.1-azocycloheptylidene-2,2-diphosphonic acid), ethane-1-amino-1,1-diphosphonate, dichloromethane-diphosphonate, etc.Phosphonoalkane carboxylic acid or their alkali metal salts include PPTA(phosphonopropane tricarboxylic acid), PBTA(phosphonobutane-1,2,4-tricarboxylic acid), each as acid or alkali metalsalts.

In addition, antimicrobial antiplaque agents may also be present in thepresent compositions. Such agents may include, but are not limited to,triclosan, 5-chloro-2-(2,4-dichlorophenoxy)-phenol, as described in TheMerck Index, 11th ed. (1989), pp. 1529 (entry no. 9573) in U.S. Pat. No.3,506,720, and in European Patent Application No. 0,251,591;chlorhexidine (Merck Index, no. 2090), alexidine (Merck Index, no. 222;hexetidine (Merck Index, no. 4624); sanguinarine (Merck Index, no.8320); benzalkonium chloride (Merck Index, no. 1066); salicylanilide(Merck Index, no. 8299); domiphen bromide (Merck Index, no. 3411);cetylpyridinium chloride (CPC) (Merck Index, no. 2024;tetradecylpyridinium chloride (TPC); N-tetradecyl-4-ethylpyridiniumchloride (TDEPC); octenidine; delmopinol, octapinol, and otherpiperidino derivatives; In addition there may be effective antimicrobialamounts of essential oils and combinations thereof for example citral,geranial, and combinations of menthol, eucalyptol, thymol and methylsalicylate; antimicrobial metals and salts thereof for example thoseproviding zinc ions, stannous ions, copper ions, and/or mixturesthereof; bisbiguanides, or phenolics; antibiotics such as augmentin,amoxicillin, tetracycline, doxycycline, minocycline, and metronidazole;and analogs and salts of the above antimicrobial antiplaque agentsand/or anti-fungals such as those for the treatment of candida albicans.If present, these agents generally are present in a safe and effectiveamount for example from about 0.1% to about 5% by weight of the presentcompositions.

In addition, the present composition may comprise a safe and effectiveamount of an anticaries agent, and mixtures thereof. The anticariesagent may be selected from the group consisting of xylitol, fluoride ionsource providing free fluoride ions, and mixtures thereof. In certainembodiments, a fluoride ion source may be selected from the groupconsisting of sodium fluoride, stannous fluoride, indium fluoride,organic fluorides such as amine fluorides, and sodiummonofluorophosphate, wherein sodium fluoride is preferred. In certainembodiments, the instant compositions provide from about 50 ppm to10,000 ppm, more preferably from about 100 to 3000 ppm, of fluoride ionsin the compositions that contact dental surfaces when used with thecomposition as disclosed herein.

In addition, coolants, desensitizing agents and numbing agents can beused as optional ingredients in compositions of the present invention,in certain embodiments at a level of from about 0.001% to about 10%,more particular from about 0.1% to about 1%, by weight of thecomposition. Coolants, desensitizing agents and numbing agents maydecrease potential negative perceptions, such as tingling, burning etc.. . . Coolant can be any of a wide variety of materials. Included amongsuch materials are carboxamides, menthol, ketals, diols, and mixturesthereof. Optional coolants in the present compositions may be theparamenthan carboxyamide agents such as N-ethyl-p-menthan-3-carboxamide(known as “WS-3”), N,2,3-trimethyl-2-isopropylbutanamide (known as“WS-23”), menthol, 3-1-menthoxypropane-1,2-diol (known as TK-10),menthone glycerol acetal (known as MGA) menthyl lactate (known asFrescolat®), and mixtures thereof. The terms menthol and menthyl as usedherein include dextro- and levorotatory isomers of these compounds andracemic mixtures thereof. Desensitizing or Anti-pain agent may include,but are not limited to, strontium chloride, potassium nitrate, naturalherbs such as gall nut, Asarum, Cubebin, Galanga, scutellaria,Liangmianzhen, Baizhi, etc. Suitable numbing agents include benzocaine,lidocaine, clove bud oil, and ethanol.

In addition, anti-inflammatory agents may be present in the multi-phaseoral compositions as disclosed herein. Such agents may include, but arenot limited to, non-steroidal anti-inflammatory agents such as aspirin,ketorolac, flurbiprofen, ibuprofen, naproxen, indomethacin, aspirin,ketoprofen, piroxicam and meclofenamic acid, COX-2 inhibitors such asvaldecoxib, celecoxib and rofecoxib, and mixtures thereof. If present,the anti-inflammatory agents generally comprise from about 0.001% toabout 5% by weight of the compositions.

In addition, nutrients, such as minerals, may improve the teeth and thetooth surface and thus can be included with the compositions asdisclosed herein. Suitable minerals are e.g. calcium, phosphorus,fluoride, zinc, manganese, potassium and mixtures thereof. Theseminerals are e.g disclosed in Drug Facts and Comparisons (loose leafdrug information service), Wolters Kluer Company, St. Louis, Mo., ©1997,pp10-17.

In addition, the compositions as disclosed herein may optionallycomprise a safe and effective amount of a flavoring agent. Suitableflavoring agents include oil of wintergreen, oil of peppermint, oil ofspearmint, clove bud oil, menthol, anethole, methyl salicylate,eucalyptol, 1-menthyl acetate, sage, eugenol, parsley oil, oxanone,alpha-irisone, marjoram, lemon, orange, propenyl guaethol, cinnamon,vanillin, thymol, linalool, cinnamaldehyde glycerol acetal (known asCGA), and mixtures thereof. If present the flavoring agents aregenerally used at levels of from about 0.01% to about 30%, in certainembodiments from about 1% to about 20%, more particular from about 1.5%to about 15%, by weight of the composition.

In addition, the present compositions may optionally comprise sweeteningagents including sucralose, sucrose, glucose, saccharin, dextrose,levulose, lactose, mannitol, sorbitol, fructose, maltose, xylitol,saccharin salts, thaumatin, aspartame, D-tryptophan, dihydrochalcones,acesulfame and cyclamate salts, especially sodium cyclamate and sodiumsaccharin, and mixtures thereof. If present, the composition containsfrom about 0.1% to about 10% of these agents, in certain embodimentsfrom about 0.1% to about 1%, by weight of the composition.

In addition, dyes, pigments, colorants, and mixtures thereof mayoptionally be included in the present composition to give thecompositions herein colored appearance. An advantage of adding pigmentsand/or colorants to the compositions herein is that it will allow theuser to see if the composition covers their teeth evenly and completely,since coverage is easier to see with a colored composition. In addition,the colorant may provide color similar to the color of bleached teeth.Colorants useful herein are stable with the bleach agent and are thoserecognized as safe. The levels of dye, pigments and colorants that areoptionally used herein are in the range of about 0.05% to about 20%, incertain embodiments from about 0.10% to about 15% and more particularfrom about 0.25% to about 5% by weight of the composition.

Bleaching Efficacy

In certain embodiments, the bleaching efficacy of the present invention,as measured per the clinical protocol, as disclosed herein andcalculated as −Δb* may be at least about, 0.25, 0.5, 1, 1.5. 2, 2.5, 3,4, 5, 6, 7, 8, 9 or 10 or any other numerical range, which is narrowerand which falls within such broader numerical range, as if such narrowernumerical ranges were all expressly written herein.

In certain embodiments, the bleaching efficacy of the present invention,as measured per the clinical protocol as disclosed herein, andcalculated as −Δb* may be at least about 0.25, preferably at least about0.5, more preferred at least about 1.0, even more preferred at leastabout 1.5, even more preferred at least about 2, even more preferred atleast about 2.5, even more preferred at least about 3, even morepreferred at least about 3.5, and even more preferred at least about 4,or any other numerical range, which is narrower and which falls withinsuch broader numerical range, as if such narrower numerical ranges wereall expressly written herein. Generally, a change in yellowness, asmeasured per the clinical protocol as disclosed herein, and calculatedas −Δb* of at least 0.25 is noticeable.

It has been found that the present invention delivers a surprisinglyhigh ratio of bleaching efficacy of the present invention, as measuredper the clinical protocol as disclosed herein, and calculated as −Δb* tothe weight percent of bleaching agent present in the overall multi-phaseoral composition.

In certain embodiments, the ratio of bleaching efficacy of the presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb* to the weight percent of bleaching agent presentin the overall multi-phase oral composition may be at least about, 0.25,0.5, 1, 1.5. 2, 2.5, 5, 10, or 15 or any other numerical range, which isnarrower and which falls within such broader numerical range, as if suchnarrower numerical ranges were all expressly written herein.

In certain embodiments, the ratio of bleaching efficacy of the presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb* to the weight percent of bleaching agent presentin the overall multi-phase oral composition may be at least about 2.5,preferably at least about 5, more preferred at least about 10, even morepreferred at least about 15.

In certain embodiments, the bleaching efficacy of the present invention,as measured per the clinical protocol, as disclosed herein andcalculated as −Δb* may be at least about 10%, at least about 100%, atleast about 1000%, or at least about 10,000% more than the bleachingefficacy of a comparative oral care composition in the form of anaqueous solution or aqueous gel. The comparative oral care compositioncomprises the same bleaching agent at the same overall concentrationdissolved into the aqueous solution or aqueous gel.

It has been found that the present invention delivers: 1) a surprisinglyhigh ratio of bleaching efficacy, as measured per the clinical protocolas disclosed herein, and calculated as −Δb* to the fraction ofparticipants who reported oral irritation or were observed to have oralirritation that was possibly or probably attributed to the compositiontested; 2) a surprisingly high ratio of bleaching efficacy of thepresent invention, as measured per the clinical protocol as disclosedherein, and calculated as −Δb* treatments to the fraction ofparticipants who reported tooth sensitivity that was possibly orprobably attributed to the composition; or 3) a surprisingly high ratioof bleaching efficacy of the present invention, as measured per theclinical protocol as disclosed herein, and calculated as −Δb* to thefraction of participants who reported tooth sensitivity or reported oralirritation or were observed to have oral irritation that was possibly orprobably attributed to the composition.

In certain embodiments, the ratio of bleaching efficacy of the presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb* to the fraction of participants who report toothsensitivity that is possibly or probably attributed to the presentinvention may be at least about 6, 7, 8, 9, 10, 15, 20, 25, 50, or 100or any other numerical range, which is narrower and which falls withinsuch broader numerical range, as if such narrower numerical ranges wereall expressly written herein.

In certain embodiments, the ratio of bleaching efficacy of the presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb* to the fraction of participants who report toothsensitivity that is possibly or probably attributed to the presentinvention may be at least about 6, preferably at least about 7, morepreferred at least about 8, even more preferred at least about 9, evenmore preferred at least about 10, even more preferred at least about 15,even more preferred at least about 20, even more preferred at leastabout 25, and even more preferred at least about 50, or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

In certain embodiments, the ratio of bleaching efficacy of the presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb* to the fraction of participants who report oralirritation or are observed to have oral irritation that is possibly orprobably attributed to the present invention may be at least about 6, 7,8, 9, 10, 15, 20, 25, 50, or 100 or any other numerical range, which isnarrower and which falls within such broader numerical range, as if suchnarrower numerical ranges were all expressly written herein.

In certain embodiments, the ratio of bleaching efficacy of the presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb* to the fraction of participants who report oralirritation or are observed to have oral irritation that is possibly orprobably attributed to the present invention may be at least about 6,preferably at least about 7, more preferred at least about 8, even morepreferred at least about 9, even more preferred at least about 10, evenmore preferred at least about 15, even more preferred at least about 20,even more preferred at least about 25, and even more preferred at leastabout 50, or any other numerical range, which is narrower and whichfalls within such broader numerical range, as if such narrower numericalranges were all expressly written herein.

In certain embodiments, the ratio of bleaching efficacy of the presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb* to the fraction of participants who report toothsensitivity or report oral irritation or are observed to have oralirritation that is possibly or probably attributed to the presentinvention may be at least about 6, 7, 8, 9, 10, 15, 20, 25, 50, or 100or any other numerical range, which is narrower and which falls withinsuch broader numerical range, as if such narrower numerical ranges wereall expressly written herein.

In certain embodiments, the ratio of bleaching efficacy of the presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb* to the fraction of participants who report toothsensitivity or report oral irritation or are observed to have oralirritation that is possibly or probably attributed to the presentinvention may be at least about 6, preferably at least about 7, morepreferred at least about 8, even more preferred at least about 9, evenmore preferred at least about 10, even more preferred at least about 15,even more preferred at least about 20, even more preferred at leastabout 25, and even more preferred at least about 50, or any othernumerical range, which is narrower and which falls within such broadernumerical range, as if such narrower numerical ranges were all expresslywritten herein.

Clinical Protocol

The bleaching efficacies of the multi-phase oral compositions aremeasured using the following clinical protocol. Per treatment group, 17to 25 participants are recruited to complete the clinical study whentesting compositions with less than about 1% bleaching agent, and 8 to25 participants when testing compositions with at least about 1%bleaching agent. Recruited participants must have four natural maxillaryincisors with all measurable facial sites. The mean baseline L* of thegroup of participants must be from 71 to 76, and the mean baseline b* ofthe group of participants must be from 13 to 18. In addition,participants with malocclusion on maxillary anterior teeth, severe oratypical intrinsic staining, such as that caused by tetracycline,fluorosis or hypo-calcification, dental crowns or restorations on thefacial surfaces of maxillary anterior teeth, self-reported medicalhistory of melanoma, current smoking or tobacco use, light-sensitivityor a pigmentation skin disorder, self-reported tooth sensitivity, orprevious tooth whitening using a professional treatment,over-the-counter kit, or investigational product, are excluded from thestudy. Participants are provided with take-home kits with Crest CavityProtection toothpaste and Oral-B Indicator soft manual toothbrush (bothfrom Procter & Gamble, Cincinnati, Ohio, USA) to be used twice a day inthe customary manner

The participants use a toothbrush (“Anchor 41 tuft white toothbrush”from Team Technologies, Inc. Morristown, Tenn., USA) to brush theirteeth with water for 30 seconds prior to being treated with themulti-phase oral composition. The maxillary anterior teeth of eachparticipant are treated with the multi-phase oral composition for 60minutes once daily using a strip of polyethylene as a delivery carrier.The polyethylene strips are 66 mm×15 mm in size and 0.0178 mm thick.From 0.6 g to 0.8 g of the multi-phase oral composition is appliedacross each strip of polyethylene prior to applying to the maxillaryanterior teeth.

If the multi-phase oral composition is used with electromagneticradiation:

-   -   1) After 50 minutes of treatment with the multi-phase oral        composition on the strip, the electromagnetic radiation is        applied toward the facial surfaces of the maxillary anterior        teeth for 10 minutes,    -   2) The electromagnetic radiation is directed toward the        maxillary anterior teeth through the strip and through the        multi-phase oral composition,    -   3) The strip needs to allow at least about 90%of the        electromagnetic radiation from 400 nm to 500 nm to pass through,        and    -   4) The electromagnetic radiation is delivered via four        fiber-optic cables (model number M71L01 from Thorlabs, Newton,        N.J., USA) connected to four high power LEDs with a peak        intensity wavelength of 455 nm (model number M455F1 from        Thorlabs, Newton, N.J., USA) as shown in FIG. 6. The four LEDs        are run at 1000 mA each using an LED Driver and Hub (model        numbers DC4104 and DC4100-HUB from Thorlabs, Newton, N.J., USA).        The exit ends of the four fiber-optic cables are mounted behind        a transparent mouthpiece to help position the electromagnetic        radiation reproducibly against the outer surface of the strip.        The exit ends of the four fiber-optic cables are about 7 mm away        from the exit surface of the mouthpiece with the electromagnetic        radiation passing through the transparent mouthpiece. The        bite-shelf of the mouthpiece is offset such that the transparent        window through which the electromagnetic radiation passes toward        the maxillary anterior teeth is 7.4 mm high. Also, the        transparent window through which the electromagnetic radiation        passes toward the maxillary anterior teeth is 40 mm long        measured linearly from end to end (not including the curvature).        The exit ends of the fiber-optic cables are positioned & angled        such that the cones of electromagnetic radiation exiting from        the fiber-optic cables are centered within the transparent        window through which the electromagnetic radiation passes toward        the maxillary anterior teeth as shown in FIG. 6. Also, the exit        ends of the four fiber-optic cables are spaced such that the the        cones of electromagnetic radiation are spaced across the length        of the transparent window through which the electromagnetic        radiation passes toward the maxillary anterior teeth as shown in        FIG. 6. The intensity of the electromagnetic radiation from 400        nm to 500 nm measured at the central axis of each cone of        electromagnetic radiation exiting at the exit surface of the        transparent window through which the electromagnetic radiation        passes toward the maxillary anterior teeth needs to be from        about 175 mW/cm² to about 225 mW/cm² as measured by the method        disclosed herein.

Once 60 minutes of the treatment with the multi-phase oral compositionis completed, the strip is removed. This treatment is applied once dailyfor a minimum of 7 days for compositions with less than about 1%bleaching agent, and a minimum of 3 days for compositions with at leastabout 1% bleaching agent.

The change in tooth color due to the treatment with the multi-phasemulti-phase oral composition is measured using the procedure describedbelow the day after the 7^(th) treatment for compositions with less thanabout 1% bleaching agent and after the 3^(rd) treatment for compositionswith at least about 1% bleaching agent.

Tooth color is measured using a digital camera having a lens equippedwith a polarizer filter (Camera model no. CANON EOS 70D from Canon Inc.,Melville, N.Y. with NIKON 55 mm micro-NIKKOR lens with adapter). Thelight system is provided by Dedo lights (model number DLH2) equippedwith 150 watt, 24V bulbs model number (Xenophot model number HL X64640),positioned about 30 cm apart (measured from the center of the externalcircular surface of one of the glass lens through which the light exitsto the other) and aimed at a 45 degree angle, such that the light pathsintersect at the vertical plane of the chin rest about 36 cm in front ofthe focal plane of the camera. Each light has a polarizing filter (Lee201 filter), and a cutoff filter (Rosco 7 mil Thermashield filter fromRosco, Stamford, Conn., USA).

At the intersection of the light paths, a fixed chin rest is mounted forreproducible repositioning in the light field. The camera is placedbetween the two lights such that its focal plane is about 36 cm from thevertical plane of the chin rest. Prior to beginning the measurement oftooth color, color standards are imaged to establish calibrationset-points. A Munsell N8 grey standard is imaged first. The whitebalance of the camera is adjusted, such that the RGB values of grey are200. Color standards are imaged to get standard RGB values of the colorchips. The color standards and grey standard are listed below (fromMunsell Color, Division of X-rite, Grand Rapids, Mich., USA). Each colorstandard is labeled with the Munsell nomenclature. To create a grid ofcolor standards they can be arranged in the following manner Thisenables multiple color standards to be contained in a single imagecaptured of the grid of color standards.

Color Standard Grid 1

7.5R 6 8 2.5R 6 10 10YR 6.5 3 POLARIZATION 5R 7 8 N 3.5 0 CHECK 7.5RP 66 10R 5 8 5YR 7 3 2.5Y 8.5 2 2.2YR 6.47 4.1 7.5YR 7 4 5YR 8 2 N 8 0 10R7 4 N 8 0 5YR 7.5 2.5 2.5Y 8 4 5YR 7 3.5 5YR 7 2.5 5YR 5 2 5YR 7.5 2 N6.5 0 N 9.5 0

Color Standard Grid 2

5YR 7.5 3.5 2.5Y 6 4 10YR 7.5 3.5 2.5R 7 8 7.5R 7 8 10YR 7.5 2 10YR 7.52.5 N 5 0 2.5R 6 8 10YR 7 2 5R 7 4 10YR 7 2.5 N 6.5 0 7.5RP 6 8 7.5R 8 45Y 8 1 7.5YR 8 2 2.2YR 6.47 4.1 N 5 0 2.5Y 8 4 10YR 7 3 N 9.5 0 10RP 7 42.5Y 7 2

Color Standard Grid 3

5R 6 10 N 8.5 0 10YR 6.5 3.5 10RP 6 10 N 8 0 7.5YR 7 3 2.5Y 3.5 0 10YR 73.5 5Y 8.5 1 5YR 8 2.5 5YR 7.5 3 5R 5 6 10YR 7.5 3 5YR 6.5 3.5 2.5YR 5 42.5Y 8 2 10YR 8 2 2.5Y 7 2 2.5R 6 6 5R 7 6 10YR 8 2.5 10R 5 6 N 6.5 07.5YR 8 3

For baseline tooth color, participants use a toothbrush (“Anchor 41 tuftwhite toothbrush” from Team Technologies, Inc. Morristown, Tenn., USA)to brush their teeth with water to remove debris from their teeth. Eachparticipant then uses cheek retractors (from Washington ScientificCamera Company, Sumner, Wash., USA; treated with at frosted matte finishat A&B Deburring Company, Cincinnati, Ohio, USA) to pull the cheeks backand allow the facial surfaces of their teeth to be illuminated. Eachparticipant is instructed to bite their teeth together such that theincisal edges of the maxillary incisors contact the incisal edges of themandibular incisors. The participants are then positioned on the chinrest at the intersection of the light paths in the center of the cameraview and the tooth images are captured. After all participants areimaged, the images are processed using image analysis software (Optimasmanufactured by Media Cybernetics, Inc. of Silver Spring, Md.). Thecentral four incisors are isolated and the average RGB values of theteeth are extracted.

After the participants have used a whitening product, but prior tocapturing participant's tooth images, the system is set to the baselineconfiguration and calibrated as previously discussed. After calibration,each participant is imaged a second time using the same procedure asbefore making sure the participant is in the same physical position asthe pre-treatment image including orientation of the teeth. The imagesare processed using the image analysis software to obtain the averageRGB values of the central four maxillary incisors. The RGB values of allof the images are then mapped into CIE L*′a*b* color space using the RGBvalues and the L*a*b* values of the color chips on the color standard.The L*a*b* values of the color chips on the color standard are measuredusing a Photo Research SpectraScan PR650 from Photo Research Inc., LAusing the same lighting conditions described for capturing digitalimages of the facial dentition. The PR650 is positioned the samedistance from the color standards as the camera. Each chip isindividually measured for L*a*b* after calibration according to themanufacturer's instructions. The RGB values are then transformed intoL*a*b* values using regression equations such as:

L*=25.16+12.02*(R/100)+11.75*(G/100)−2.75*(B/100)+1.95*(G/100)³

a*=−2.65+59.22*(R/100)−50.52*(G/100)+0.20*(B/100)−29.87*(R/100)²+20.73*(G/100)²+8.14*(R/100)³−9.17(G/100)³+3.64*[(B/100)²]*[R/100]

b*=−0.70+37.04*(R/100)+12.65*(G/100)−53.81*(B/100)−18.14*(R/100)²+23.16*(G/100)*(B/100)+4.70*(R/100)³−6.45*(B/100)³

The R² for L*, a*, and b* should be >0.95. Each study should have itsown equations.

These equations are generally valid transformations in the area of toothcolor (60<L*<95, 0<a*<14, 6<b*<25). The data from each participant's setof images is then used to calculate product whitening performance interms of changes in L*, a* and b*—a standard method used for assessingwhitening benefits. When evaluating compositions with less than about 1%bleaching agent: Changes in L* is defined asΔL*=L*_(day after 7 treatments)−L*_(baseline) where a positive changeindicates improvement in brightness; Changes in a* (red-green balance)is defined as Δa*=a*_(day after 7 treatments)−a*_(baseline) where anegative change indicates teeth which are less red; Changes in b*(yellow-blue balance) is defined asΔb*=b*_(day after 7 treatments)−b*_(baseline) where a negative changeindicates teeth are becoming less yellow. When evaluating compositionswith at least about 1% bleaching agent: Changes in L* is defined asΔL*=L*_(after 3 treatments)−L*_(baseline) where a positive changeindicates improvement in brightness; Changes in a* (red-green balance)is defined as Δa*=a*_(after 3 treatments)−a*_(baseline) where a negativechange indicates teeth which are less red; Changes in b* (yellow-bluebalance) is defined as Δb*=b*_(after 3 treatments)−b*_(baseline) where anegative change indicates teeth are becoming less yellow. −Δb* is usedas the primary measure of bleaching efficacy. The overall color changeis calculated by the equation

ΔE=(ΔL* ² +Δa* ² +Δb* ²)^(1/2).

After using the whitening products, color changes in CIE Lab color spacecan be calculated for each participant based on the equations given.

To validate the above clinical protocol, the bleaching efficacy(calculated as −Δb*) of Example-IA (delivered on a strip and used withelectromagnetic radiation as disclosed herein) needs to be measured theday after the 7^(th) treatment and demonstrated to be >0.5.

Optional Application Systems

In addition, the present invention may further relate to a deliverysystem for delivering the present compositions to the tooth surface. Forexample, in certain embodiments the compositions of the presentinvention may deliver whitening benefits to the oral cavity by beingdirectly applied to the teeth without using a delivery carrier system.In addition, in certain embodiments the present invention may include adelivery system comprising the present compositions in combination witha delivery carrier. For example, the delivery system may comprise afirst layer of a carrier material and a second layer comprising amulti-phase oral composition described herein, whereby the bleachingagent is releasably located within the present composition. A suitablefirst layer may comprise a delivery carrier including a strip ofmaterial, a dental tray, a sponge material, and mixtures thereof. Incertain embodiments, the delivery carrier may be a strip of material,such as a permanently deformable strip. Suitable strips of material orpermanently deformable strips are for example disclosed in U.S. Pat.Nos.; 6,136,297; 6,096,328; 5,894,017; 5,891,453; and 5,879,691; and inU.S. Pat. Nos. 5,989,569 and 6,045,811; and in patent application US2014/0178443 A1.

The delivery carrier may be attached to the teeth via an attachmentmeans that is part of the delivery carrier, for example the deliverycarrier may be of sufficient size that, once applied the deliverycarrier overlaps with the oral soft tissues rendering more of the teethsurface available for bleaching. The delivery carrier may also beattached to the oral cavity by physical interference or mechanicalinter-locking between the delivery carrier and the oral surfacesincluding the teeth.

The delivery carrier maybe transparent or translucent to electromagneticradiation with wavelengths from about 200 nm to about 1700 nm. Incertain embodiments, the delivery carrier allows from about 10%, 20%, or30% to about 40%, 50%, 60%, 70%, 80%, 90%, or 100% of electromagneticradiation from about 400 nm to about 500 nm to pass through.

Where the delivery carrier is a strip of material, the second layercomposition may be coated on the strip, or be applied by the user to thestrip, or be applied by the user to the teeth and then the strip may beplaced over the coated teeth. The amount of composition applied to thestrip or teeth may depend upon the size and capacity of the strip,concentration of the active and the desired benefit; for example fromabout 0.0001, 0.001 or 0.01 grams to about 0.01, 0.1, 1, or 5 grams maybe used or any other numerical range, which is narrower and which fallswithin such broader numerical range, as if such narrower numericalranges were all expressly written herein, of composition, in particularfrom about 0.001 g to about 0.5 g or from about 0.1 g to about 0.4 g ofmulti-phase oral composition may be used. In addition, from about0.0001, 0.001 or 0.01 grams to about 0.01, 0.1, 0.5, or 1 gramscomposition per square centimeter of material (g/cm²) may be used or anyother numerical range, which is narrower and which falls within suchbroader numerical range, as if such narrower numerical ranges were allexpressly written herein; in certain embodiments less than about 0.2g/cm², from about 0.0001 g/cm² to about 0.1 g/cm², or from about 0.01g/cm² to about 0.04 g/cm². In addition, or alternatively, from about 1microgram to about 5000 micrograms bleaching agent per square centimeterof material (microgram/cm2), preferably from about 10 micrograms/cm2 toabout 500 micrograms/cm2, and more preferably from about 50micrograms/cm2 to about 100 micrograms/cm2 bleaching agent per squarecentimeter of material may be used.

Referring now to the drawings, and more particularly to FIG. 1, there isshown an embodiment of a suitable delivery system 10, representing adelivery system for delivering bleach actives provided by a multi-phaseoral composition as disclosed herein to the teeth and the oral cavity.Delivery system 10 comprises a material in strip form 12 of materialwhich is substantially flat, and may have rounded corners. Onto saidstrip 12 a second layer 14 comprising the present multi-phase oralcomposition is releasably applied. The second layer 14 may be homogenousand may be uniformly and evenly coated onto strip 12, as shown in thecross-sectional view of FIG. 2. In addition, the second layer 14comprising the present compositions may be a coating only along alongitudinal axis of a portion of strip of material 12 or may be appliedas stripes, spots, and/or other patterns. However, in certainembodiments the second layer 14 may be a laminate or separated layers ofcomponents, an amorphous mixture of components, separate stripes orspots or other patterns of different components, or a combination ofthese structures, including a coating of the second layer 14 along alongitudinal axis of a portion of the strip of material 12.

In certain embodiments, the second layer 14 may contain or is itself anactive, such as a composition, compound, or mixture capable ofinfluencing or effecting a desired change in appearance or structure ofthe surface it contacts. As discussed previously, example activesinclude: hydrogen peroxide, carbamide peroxide, sodium fluoride, sodiummonofluorophosphate, pyrophosphate, chlorhexidine, polyphosphate,triclosan, and enzymes. Examples of appearance and structural changesinclude, but are not necessarily limited to: whitening, stain bleaching,stain removal, remineralization to form fluorapatite, plaque removal,and tartar removal.

In addition, the second layer 14 composition may comprise adhesive meansin order to stably attach the delivery system 10 to the tooth surface.In certain embodiments, the composition as disclosed herein may providethe intended stickiness and adhesiveness by its own, for example bychoosing a hydrophobic phase which already provides adhesive propertiesby adding adhesive material to the compositions of the presentinvention, or both. In certain embodiments, if added, an adhesive mayprovide additional properties, such as thickening/rheology modifyingproperties.

FIGS. 3 and 4 show a delivery system 10 of the present invention appliedto the tooth surface of a plurality of adjacent teeth. Embedded inadjacent soft tissue 20 is a plurality of adjacent teeth 22. Adjacentsoft tissue 20 herein defined as soft tissue surfaces surrounding thetooth structure including: papilla, marginal gingival, gingivalsulculus, inter dental gingival, and gingival gum structure on lingualand buccal surfaces up to and including muco-gingival junction on thepallet.

In both FIGS. 3 and 4, delivery system 10 represents a strip 12 andsecond layer 14 comprising the present composition, wherein the secondlayer 14 is located on the side of strip of material 12 facing teeth 22.Composition of second layer 14 may be pre-applied to strip of material12, or may be applied to strip of material 12 by the user prior toapplication to the teeth. Alternatively, the composition of second layer14 may be applied directly to teeth 22 by the user and then covered by astrip 12. In any case, strip of material 12 may have a thickness andflexural stiffness such that it can conform to the contoured surfaces ofteeth 22 and to adjacent soft tissue 20. Thus, the strip of material 12may have sufficient flexibility to form to the contours of the oralsurface, the surface being a plurality of adjacent teeth 22. The strip12 may also readily conformable to tooth surfaces and to theinterstitial tooth spaces without permanent deformation when thedelivery system 10 is applied. The delivery system 10 can be appliedwithout significant pressure.

The first layer 12 of the delivery system 10 may be comprised of a stripof material. Such first layer materials are described in more detail inU.S. Pat. Nos; 6,136,297; 6,096,328; 5,894,017; 5,891,453; and5,879,691; and in U.S. Pat. Nos. 5,989,569 and 6,045,811; and in patentapplication US 2014/0178443 A1. The strip 12 serves as a protectivebarrier for the bleaching agent in the second layer 14. It preventsleaching or erosion of the second layer 14 by for example, the wearer'stongue, lips, and saliva. This allows the active agent in the secondlayer 14 to act upon the tooth surfaces 22 of the oral cavity for theintended period of time, for example from several minutes to severalhours.

The following description of strip of material may apply to the deliverysystems 10 with the strip layer 12 as shown in FIGS. 1 to 4 or any formof strips. The strip of material may comprise polymers, natural andsynthetic woven materials, non-woven material, foil, paper, rubber andcombinations thereof. The strip of material may be a single layer ofmaterial or a laminate of more than one layer. Regardless of the numberof layers, the strip of material may be substantially water insoluble.The strip material may also be water impermeable. Suitable stripmaterial may be any type of polymer or combination of polymers that meetthe required flexural rigidity and are compatible with oral caresubstances. Suitable polymers include, but are not limited to,polyethylene, ethylvinylacetate, polyesters, ethylvinyl alcohol andcombinations thereof. Examples of polyesters include Mylar® andfluoroplastics such as Teflon®, both manufactured by Dupont. In certainembodiments, the material used as strip of material is polyethylene. Thestrip of material may be less than about 1 mm (millimeter) thick, lessthan about 0.05 mm thick, or from about 0.001 to about 0.03 mm thick. Apolyethylene strip of material may be less than about 0.1 mm thick orfrom about 0.005 to about 0.02 mm thick.

In certain embodiments, the present invention may comprise a dissolvablefilm, which can be adhered to the oral cavity thereby releasing anactive, the dissolvable film comprising water-soluble polymers, one ormore polyalcohols, and one or more actives. In addition to one or moreactives, a dissolvable film may contain a combination of certainplasticizers or surfactants, colorants, sweetening agents, flavors,flavor enhancers, or other excipients commonly used to modify the tasteof formulations intended for application to the oral cavity. Theresulting dissolvable film is characterized by an instant wettabilitywhich causes the dissolvable film to soften soon after application tothe mucosal tissue, thus preventing the user from experiencing anyprolonged adverse feeling in the mouth, and a tensile strength suitablefor normal coating, cutting, slitting, and packaging operations.

The dissolvable film may comprise a water-soluble polymer or acombination of water-soluble polymers, one or more plasticizers orsurfactants, one or more polyalcohols, and an active.

The polymers used for the dissolvable film include polymers which arehydrophilic and/or water-dispersible. Examples of polymers that can beused include polymers that are water-soluble cellulose-derivatives, suchas hydroxypropylmethyl cellulose, hydroxyethyl cellulose, orhydroxypropyl cellulose, either alone, or mixtures thereof. Otheroptional polymers, without limiting the invention, include polyvinylpyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodiumalginate, polyethylene glycol, natural gums like xanthane gum,tragacantha, guar gum, acacia gum, arabic gum, water-dispersiblepolyacrylates like polyacrylic acid, methylmethacrylate copolymer,carboxyvinyl copolymers. The concentration of the water-soluble polymerin the final film can very between 20 and 75% (w/w), or between 50 and75% (w/w).

The surfactants that may be used for the dissolvable film may be one ormore nonionic surfactants. When a combination of surfactants is used,the first component may be a polyoxyethylene sorbitan fatty acid esteror a ALPHA-hydro-OMEGA-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer, whilethe second component may be a polyoxyethylene alkyl ether or apolyoxyethylene castor oil derivative. In certain embodiments, the HLBvalue of the polyoxyethylene sorbitan fatty acid ester should be between10 and 20, whereby a range of 13 to 17 may also be used. TheALPHA-hydro-OMEGA-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer may contain at least about 35oxypropylene-units, and in certain embodiments not less than about 50oxypropylene-units.

The polyoxyethylene alkyl ether may an HLB value between 10 and 20, andin certain embodiments an HLB value of not less than 15 may be used. Thepolyoxyethylene castor oil derivative may have an HLB value of 14-16.

In order to achieve the desired instant wettability, the ratio betweenthe first and second component of the binary surfactant mixture may bekept within 1:10 and 1:1, or between 1:5 and 1:3.

The total concentration of surfactants in the dissolvable film dependson the properties of the other ingredients, but usually may be between0.1 and 5% (w/w).

The polyalcohol can be used to achieve a desired level of softness ofthe dissolvable film. Examples of polyalcohols include glycerol,polyethylene glycol, propylene glycol, glycerol monoesters with fattyacids or other pharmaceutically used polyalcohols. The concentration ofthe polyalcohol in the dry film usually ranges between 0.1 and 5% (w/w).

The shape of the strip of material may be any shape or size that coversthe desired oral surface. For example, in certain embodiments the stripof material may have rounded corners to avoid irritation of the softtissue of the oral cavity. “Rounded corners,” as used herein means nothaving any sharp angles or points, for example one or more angles of135° or less. The length of the strip of material may be from about 2 cm(centimeter) to about 12 cm, or from about 4 cm to about 9 cm. The widthof the strip of material may also depend on the oral surface area to becovered. The width of the strip of material may be from about 0.5 cm toabout 4 cm or from about 1 cm to about 2 cm. The strip or material maybe worn as a patch on one or several teeth to treat a localizedcondition.

The strip of material may contain shallow pockets. When the multi-phaseoral composition is coated on a strip of material, bleach agents and/ororal care actives, fill shallow pockets to provide reservoirs ofadditional bleach agents and/or oral care actives. Additionally theshallow pockets help to provide texture to the delivery system. Thestrip of material may have an array of shallow pockets. Generally theshallow pockets are approximately 0.4 mm across and about 0.1 mm deep.When shallow pockets are included in the strip of material andmulti-phase oral compositions herein are applied to it in variousthicknesses, in certain embodiments the overall thickness of thedelivery system is less than about 1 mm, in certain embodiments theoverall thickness is less than about 0.5 mm

Flexural stiffness is a material property that is a function of acombination of strip of material thickness, width and material modulusof elasticity. The test described below is a method for measuring therigidity of films, such as polyolefin film and sheeting. It determinesthe resistance to flexure of a sample by using a strain gauge affixed tothe end of a horizontal beam. The opposite end of the beam pressesacross a strip of the sample to force a portion of the strip into avertical groove in a horizontal platform upon which the sample rests. Amicroammeter wired to the strain gauge is calibrated in terms ofdeflection force. The rigidity of the sample is read directly from themicroammeter and expressed as grams per centimeter of the sample stripwidth. In certain embodiments, a strip of material which is suitable tobe used as delivery carrier of the compositions as disclosed herein mayshow a flexural stiffness of less than about 5 grams/cm as measured on aHandle-O-Meter, model #211-300, available from Thawing-Albert InstrumentCompany of Philadelphia, Pa. as per test method ASTM D2923-95. The stripmay have a flexural stiffness less than about 3 grams/cm, less thanabout 2 grams/cm or a flexural stiffness from about 0.1 to about 1grams/cm. Generally, the flexural stiffness of the strip of material maybe substantially constant and does not change during normal use. Forexample, the strip of material does not need to be hydrated for thestrip to achieve the low flexural stiffness in the above-specifiedranges. This relatively low stiffness enables the strip of material tocover the contours of the oral surface with very little force beingexerted. That is, conformity to the contours of the oral surface of thewearer's mouth is maintained because there is little residual forcewithin the strip of material to cause it to return to its shape justprior to its application to the oral surface, i.e. substantially flat.For example, in certain embodiments a strip of material's flexibilityenables it to contact soft tissue over an extended period of timewithout irritation; such that a strip of material does not requirepressure for retention against the oral surface.

The delivery systems as used herein may comprise an adhesion means, suchthat they are capable of adhesion to oral surfaces, especially theteeth. This adhesion means may be provided by the present compositionsherein or the adhesion means may be provided independently of thecompositions herein (for example the adhesion means is a separate phasefrom the compositions herein where the compositions may also have anadhesive means). In certain embodiments, the strip of material may beheld in place on the oral surface by adhesive attachment provided by thepresent composition. The viscosity and general tackiness of themulti-phase oral composition to dry surfaces may cause the strip to beadhesively attached to the oral surface without substantial slippagefrom the frictional forces created by the lips, teeth, tongue, and otheroral surfaces rubbing against the strip of material while talkingdrinking, etc. However, this adhesion to the oral surface may be lowenough to allow the strip of material to be easily removed by the wearerby simply peeling off the strip of material using one's finger. Thedelivery system may be easily removable from the oral surfaces withoutthe use of an instrument, a chemical solvent or agent or excessfriction.

In addition, in certain embodiments the strip of material may be held inplace on the oral surface by adhesive means and attachment provided bythe delivery carrier itself. For example, the strip of material canextend, attach, and adhere to the oral soft tissue. In addition, incertain embodiments an adhesive can be applied to that portion of thestrip of material that will attach the delivery systems to the oral softtissue. The delivery carrier may also be attached to the oral cavity byphysical interference or mechanical inter-locking between the deliverycarrier and the oral surfaces including the teeth. In addition, thestrip of material may be held in place by an adhesion means that isindependent of the composition of the present inventions herein, asdisclosed in WO 03/015656.

Suitable adhesion means are known to the skilled person. When theadhesive means, if present, is provided by an adhesive, the adhesive maybe any adhesive which may be used to adhere materials to the toothsurface or to a surface of the oral cavity surfaces. Suitable adhesivesinclude, but are not limited to, skin, gum and muco adhesives, andshould be able to withstand the moisture, chemicals and enzymes of theoral environment for long enough for the oral care actives and/or bleachto take effect, but may be soluble and/or biodegradable thereafter.Suitable adhesives may for example comprise water soluble polymers,hydrophobic and/or non-water soluble polymers, pressure and moisturesensitive adhesives, e.g. dry adhesives which become tacky upon contactwith the mouth environment, e.g. under the influence of moisture,chemicals or enzymes etc. in the mouth. Suitable adhesives includenatural gums, synthetic resins, natural or synthetic rubbers, those gumsand polymers listed above under “Thickening Agents”, and various othertacky substances of the kind used in known adhesive tapes, those knownfrom U.S. Pat. No. 2,835,628.

The delivery carrier, such as a strip, as shown for example in FIGS. 1to 4, may be formed by several of the film making processes known in theart. For example, a strip of polyethylene is made by a blown process ora cast process. Other processes including extrusion or processes that donot affect the flexural rigidity of the strip of material are alsofeasible. In addition, the present compositions forming a second layeronto the strip may be incorporated onto the strip during the processingof the strip and/or the present composition may be a laminate layer onthe strip. The second layer attached to the strip of such a deliverysystem as disclosed above comprises a safe and effective amount of thepresent composition described herein.

In addition, the delivery system may comprise an optional release liner.Such a release liner may be formed from any material which exhibits lessaffinity for the second layer composition than the second layercomposition exhibits for itself and for the first layer strip ofmaterial. The release liner may comprise a rigid sheet of material suchas polyethylene, paper, polyester, or other material, which is thencoated with a nonstick type material. The release liner may be cut tosubstantially the same size and shape as the strip of material or therelease liner may be cut larger than the strip of material to provide areadily accessible means for separating the material from the strip. Therelease liner may be formed from a brittle material that cracks when thestrip is flexed or from multiple pieces of material or a scored piece ofmaterial. Alternatively, the release liner may be in two overlappingpieces such as a typical adhesive bandage design. A description ofmaterials suitable as release agents is found in Kirk-Othmer,Encyclopedia of Chemical Technology, Fourth Edition, Volume 21, pp.207-218, incorporated herein by reference.

In certain embodiments, the delivery carrier may be a permanentlydeformable strip of material having a yield point and thickness suchthat the strip of material substantially conforms to a shape of a toothvia permanent deformation under a pressure less than about 250,000Pascals as it has been found that wearers will press a strip onto eachtooth using one fingertip having about one square centimeter surfacearea. They typically apply force at each tooth for one second or lesswith a typical application pressure ranging from about 100,000 Pascalsto about 250,000 Pascals.

In certain embodiments, a strip of material has visco-elastic propertieswhich enable it to creep as well as bend in order to conform acrossseveral teeth and around the arch of the wearer's mouth. It is importantthat the necessary permanent deformation occurs under minimum normalforce being applied by the wearer.

The multi-phase oral composition may also be applied to the toothsurface and may be covered with the deformable strip before or after ithas been shaped. In addition or alternatively, the multi-phase oralcomposition may be applied to the deformable strip as pre-coating andmay be applied together with the strip to the tooth surface before orafter the deformable strip has been shaped, wherein the strip is appliedsuch that when the delivery system is placed on a surface of the tooth,the multi-phase oral composition contacts the tooth surface providing anactive onto the tooth surface. In addition or alternatively, thedeformable strip of material may be applied to the teeth with a forcesufficient to shape the delivery carrier such that it at least partiallyconforms to the shape of the teeth, then the shaped strip of materialmay be removed from the tooth surface, the oral care composition may beapplied to the shaped strip of material, and the shaped strip ofmaterial may be re-applied to the tooth surface such that it at leastpartially conforms to a shape of the tooth and contacts the oral carecomposition against the tooth surface. If the deformable strip isapplied together with the multi-phase oral composition to the toothsurface the multi-phase oral composition may also comprise adhesiveagents to hold the delivery system in place for a sufficient time toallow the active of the multi-phase oral composition to act upon thesurface. The multi-phase oral composition, if used together with adeformable strip, may have an extrusion resistance sufficient towithstand a normal force applied to shape the deformable strip ofmaterial so that the substance is not substantially extruded frombetween the deformable strip of material and the surface during manualshaping of the deformable strip of material. By “substantially extrudedfrom” is meant that at least 50% or more of the multi-phase oralcomposition is extruded from between the deformable strip of materialand the tooth and adjoining soft tissue surfaces.

The deformable strip of material may be made of a permanently deformablematerial, such as wax, putty, tin or foil, as a single layer or acombination of layers or materials, such as a laminate. In certainembodiments, the deformable strip may be wax, such as #165 sheet waxformulated and manufactured by Freeman Mfg. & Supply Co. of Cleveland,Ohio. This particular wax readily conforms to the shape of a tooth undera pressure of about 133,000 Pascal which is the pressure generated whenthe wearer applies a normal force of about 3 pounds (1.36 kg) over anarea of about one square centimeter. The deformable strip of materialmay have a nominal film thickness of about 0.8 mm, wherein thedeformable strip may be substantially flat and rectangular in shape withrounded corners. The deformable strip of material may have a lengthsufficient to cover a plurality of adjacent teeth while conforming tothe curvature of the wearer's mouth and gaps between the adjacent teeth.If the deformable strip of material includes the multi-phase oralcomposition coated thereon, the multi-phase oral composition may have anoverall thickness less than about 1.5 mm Deformable strips as disclosedherein may also be used as the material for the strip of material 12shown in FIGS. 1 to 4. Thus, general features of a strip of material asdescribed above for example with respect to FIGS. 1 to 4 may also applyto the deformable strip of material. In addition, a release liner and/orshallow pockets may also be combined with a deformable strip ofmaterial.

Alternatively, the present compositions may be used in combination witha delivery carrier including a dental tray and/or foam material. Dentaltrays are well known in the whitening art and an example dental tray 30is shown in FIG. 5. The general process for preparing dental trays 30 isknown in the art. Dentists have traditionally utilized three types ofdental appliances for bleaching teeth.

The first type is a rigid appliance which is fitted precisely to thepatient's dental arches. For example, an alginate impression whichregisters all teeth surfaces plus gingival margin is made and a cast ispromptly made of the impression. If reservoirs are desired they areprepared by building a layer of rigid material on the cast on specificteeth surfaces to be treated. A dental tray is then vacuum formed fromthe modified cast using conventional techniques. Once formed, the trayis preferably trimmed barely shy of the gingival margin on both buccaland lingual surfaces. Enough tray material should be left to assure thatall of the tooth will be covered to within about ¼ to about ⅓ mm of thegingival border upon finishing and beveling the tray periphery. One canscallop up and around interdental papilla so that the finished tray doesnot cover them. All tray edges are preferably smoothed so that the lipand tongue will not feel an edge prominence. The resulting tray,provides a perfect fit of the patient's teeth optionally with reservoirsor spaces located where the rigid material was placed on the cast.Dental trays may comprise of soft transparent vinyl material having apreformed thickness from about 0.1 cm to about 0.15 cm. Soft material ismore comfortable for the patient to wear. Harder material (or thickerplastic) may also be used to construct the tray.

A second type of rigid custom dental appliance is an “oversized” rigidcustom dental appliance. The fabrication of rigid, custom dentalappliances entails fabricating cast models of the patient's dental archimpressions, and heating and vacuum-forming a thermoplastic sheet tocorrespond to the cast models of a patient's dental arches.Thermoplastic films are sold in rigid or semi rigid sheets, and areavailable in various sizes and thickness. The dental laboratoryfabrication technique for the oversized rigid dental appliance involvesaugmenting the facial surfaces of the teeth on the cast models withmaterials such as die spacer or light cured acrylics. Next,thermoplastic sheeting is heated and subsequently vacuum formed aroundthe augmented cast models of the dental arch. The net effect of thismethod results in an “oversized” rigid custom dental appliance.

A third type of rigid custom dental appliance, used with less frequency,is a rigid bilaminated custom dental appliance fabricated fromlaminations of materials, ranging from soft porous foams to rigid,non-porous films. The non-porous, rigid thermoplastic shells of thesebilaminated dental appliances encase and support an internal layer ofsoft porous foam.

A fourth type of dental tray replaces rigid custom dental applianceswith disposable U-shaped soft foam trays, which may be individuallypackaged, and which may be saturated with a pre-measured quantity of thecomposition of the present invention. The soft foam material isgenerally an open celled plastic material. Such a device is commerciallyavailable from Cadco Dental Products in Oxnard, Calif. under thetradename VitalWhite™. These soft foam trays may comprise a backingmaterial (e.g. a closed cell plastic backing material) to minimize theelution of the bleaching agent from the device, into the oral cavity tominimize ingestion by the patient and/or irritation of the oral cavitytissues. Alternatively, the soft foam tray is encased by a nonporousflexible polymer or the open cell foam is attached to the frontal innerwall of the dental appliance and/or the open cell foam is attached tothe rear inner wall of the dental appliance. Those of ordinary skill inthe art will readily recognize and appreciate, that the presentcompositions must be thick enough not to simply run out between the opencell structure of the foam and must be thin enough to slowly passthrough the open cell foam over time. In other words, the open cell foammaterial has an internal structural spacing sized relative to theviscosity of the compositions to absorb and allow the composition topass there through.

An example of a closed cell material is a closed-cell polyolefin foamsold by the Voltek division of Sekisui America Corporation of Lawrence,Mass. under the tradename Volora which is from 1/32″ to ⅛″ in thickness.A closed cell material may also comprise of a flexible polymericmaterial. An example of an opened cell material is an open celledpolyethylene foam sold by the Sentinel Foam Products division ofPackaging Industries Group, Inc. of Hyannis, Mass. under the tradenameOpcell which is from 1/16″ to ⅜″ in thickness. Other open cell foamuseful herein include hydrophilic open foam materials such as hydrogelpolymers (e.g Medicell™ foam available from Hydromer, Inc. Branchburg,J.J.). Open cell foam may also be hydrophilic open foam material imbibedwith agents to impart high absorption of fluids, such as polyurethane orpolyvinylpyrrolidone chemically imbibed with various agents.

Preparation of the Present Multi-Phase Oral Compositions

Principally, preparation of emulsions is well known in the art and anysuitable manufacturing process can be used to make the multi-phase oralcompositions which may be in the form of an emulsion; see for example,Remmingtion: the Science and Practice of Pharmacy, 19^(th) ed., Vol. II,Chapters 20, 80, 86, etc. Generally, the components are separated intothose that are oil-soluble and those that are water-soluble. These aredissolved in their respective solvents by heating if necessary. The twophases are then mixed and the product is stirred and cooled. Aftercombining the phases, the present multi-phase oral compositions, whichmay be in the form of emulsions may be agitated or sheared by variousmethods, including shaking, intermittent shaking, high shear mixing, orby using high speed mixers, blenders, colloid mills, homogenizers, orultrasonic techniques. Various test methods are available to confirm thetype of multi-phase oral compositions, which may be in the form of anemulsion were prepared. These test methods include the dilution test,conductivity test, microscopy, and the dye-solubility test methods.Further description of test methods are disclosed in Remington: TheScience and Practice of Pharmacy, 19^(th) ed., volume 1, 1995, pp.282-283.

In certain embodiments, multi-phase oral compositions, which may be inthe form of an emulsion, as disclosed herein may be made as follows:dissolve the bleach active in the aqueous phase; then combine theaqueous phase and the hydrophobic phase in a mixing vessel and mix wellwith any means known within the art, for example, a Speedmixer (fromFlacktek Inc., Landrum, S.C.) may be used to make multi-phase oralcompositions, which may be in the form of an emulsion, of the presentinvention. The mixing procedure of the SpeedMixer™ series is based onthe double rotation of the mixing cup using a dual asymmetriccentrifugal mixing. This combination of centrifugal forces acting ondifferent levels enables very rapid mixing of the entire cup. Optionallythe composition may be heated, if necessary to facilitate solving of thebleaching active or the mixing. Continue mixing the composition untiluniform. When the active is included in solid particulate form, theaddition of an optional viscosity modifier, such as silica, may beappropriate to keep the particulate dispersed and suspended within thecomposition. Flavorants or sweeteners may also be added to one of thephases of the composition, as desired. Thereafter the composition may beadded to the delivery carrier, as desired.

MULTI-PHASE ORAL COMPOSITION FORMULATION EXAMPLES

The following non-limiting Formulation examples further describeembodiments within the scope of the present invention. Many variationsof these examples are possible without departing from the scope of theinvention.

Formulation Examples I

Formulation Examples I can be made using any suitable proceduredisclosed above and formulated with a 35% aqueous solution of hydrogenperoxide. These examples illustrate compositions that can be madewith 1) the concentration of H2O2 in the overall composition rangingfrom 0.001% to 0.0875%, and 2) the ratio of the concentration in weightpercent of H₂O₂ present in the aqueous phase to the concentration inweight percent of H₂O₂ present in the overall composition ranging from400 to 34483.

Formulation Examples I A B C D E F G (Wt %) (Wt %) (Wt %) (Wt %) (Wt %)(Wt %) (Wt %) 35% aqueous 0.25 0.20 0.15 0.10 0.05 0.0286 0.0029solution H₂O₂ ¹⁵ Petrolatum¹⁶ 99.75 99.80 99.85 99.90 99.95 99.971499.9971 total 100.00 100.00 100.00 100.00 100.00 100.00 100.00 % H₂O₂ in0.0875 0.07 0.0525 0.035 0.0175 0.01 0.001015 total oral compos. RATIO*400 500 667 1000 2000 3500 34483 *RATIO of the concentration in weightpercent of H₂O₂ present in the aqueous phase to the concentration inweight percent of H₂O₂ present in the overall composition ¹⁵ultraCosmetic Grade from Solvay, Houston, Texas ¹⁶G-2191 Grade fromSonneborn, LLC., Parsippany, NJ

Formulation Examples II

Formulation Examples II can be made using any suitable proceduredisclosed above and formulated with a 50% aqueous solution of hydrogenperoxide. These examples illustrate compositions that can be madewith 1) the concentration of H2O2 in the overall composition rangingfrom 0.0015% to 0.1%, and 2) the ratio of the concentration in weightpercent of H₂O₂ present in the aqueous phase to the concentration inweight percent of H₂O₂ present in the overall composition ranging from500 to 34483.

Formulation Examples II A B C D E F (Wt %) (Wt %) (Wt %) (Wt %) (Wt %)(Wt %) 50% aqueous 0.20 0.15 0.10 0.05 0.0286 0.0029 sol. H₂O₂Petrolatum¹⁷ 99.8 99.85 99.90 99.95 99.9714 99.9971 total 100.0 100.0100.0 100.0 100.0 100.0 % H₂O₂ in 0.10 0.075 0.05 0.025 0.0143 0.00145total compos. RATIO* 500 667 1000 2000 3500 34483 *RATIO of theconcentration in weight percent of H₂O₂ present in the aqueous phase tothe concentration in weight percent of H₂O₂ present in the overallcomposition ¹⁷G-2191 Grade from Sonneborn, LLC., Parsippany, NJ

Formulation Examples III

Formulation Examples III can be made using any suitable proceduredisclosed above and formulated with a 17.5% aqueous solution of hydrogenperoxide. These examples illustrate compositions that can be madewith 1) the concentration of H2O2 in the overall composition rangingfrom 0.0088% to 0.0875%, and 2) the ratio of the concentration in weightpercent of H₂O₂ present in the aqueous phase to the concentration inweight percent of H₂O₂ present in the overall composition ranging from200 to 2000.

Formulation Examples III A B C D E F (Wt %) (Wt %) (Wt %) (Wt %) (Wt %)(Wt %) 17.5% aqueous 0.5 0.4 0.3 0.2 0.1 0.05 sol. H₂O₂ ¹⁸ Petrolatum¹⁹99.5 99.6 99.7 99.8 99.9 99.95 total 100.0 100.0 100.0 100.0 100.0 100.0% H₂O₂ in 0.0875 0.07 0.0525 0.035 0.0175 0.0088 total compos. RATIO*200 250 333 500 1000 2000 *RATIO of the concentration in weight percentof H₂O₂ present in the aqueous phase to the concentration in weightpercent of H₂O₂ present in the overall composition ¹⁸ultra CosmeticGrade from Solvay (Houston, Texas) diluted with water ¹⁹G-2191 Gradefrom Sonneborn, LLC., Parsippany, NJ

Formulation Examples IV

Formulation Examples IV can be made using any suitable proceduredisclosed above and formulated with an 8.75% aqueous solution ofhydrogen peroxide. These examples illustrate compositions that can bemade with 1) the concentration of H2O2 in the overall compositionranging from 0.0044% to 0.099995%; and 2) the ratio of the concentrationin weight percent of H₂O₂ present in the aqueous phase to theconcentration in weight percent of H₂O₂ present in the overallcomposition ranging from 87.5 to 2000.

Formulation Examples IV A B C D E F G H (Wt %) (Wt %) (Wt %) (Wt %) (Wt%) (Wt %) (Wt %) (Wt %) 8.75% aqueous 1.1428 1.0 0.8 0.6 0.4 0.2 0.10.05 sol. H₂O₂ ²⁰ Petrolatum²¹ 98.8572 99.0 99.2 99.4 99.6 99.8 99.999.95 total 100.0 100.0 100.0 100.0 100.0 100.0 100.0 100.0 % H₂O₂ in0.099995 0.0875 0.07 0.0525 0.035 0.0175 0.0088 0.0044 total compos.RATIO* 87.50 100 125 167 250 500 1000 2000 *RATIO of the concentrationin weight percent of H₂O₂ present in the aqueous phase to theconcentration in weight percent of H₂O₂ present in the overallcomposition ²⁰ultra Cosmetic Grade from Solvay (Houston, Texas) dilutedwith water ²¹G-2191 Grade from Sonneborn, LLC., Parsippany, NJ

Formulation Examples V

Formulation Examples V can be made using any suitable proceduredisclosed above and formulated with a 35% aqueous solution of hydrogenperoxide. These examples illustrate compositions that can be madewith 1) various hydrophobic phases; and 2) various fillers.

Formulation Examples V A B C D E F (Wt %) (Wt %) (Wt %) (Wt %) (Wt %)(Wt %) 35% aqueous 0.2857 0.2857 0.2857 0.2857 0.2857 0.2857 sol. H₂O₂²² Petrolatum²³ 49.7143 79.7143 89.7143 99.6143 Mineral oil²⁴ 69.714339.7143 Polyethylene²⁵ 20.00 Microcrystalline 50.00 Wax²⁶ Polyethylene50.0000 particles²⁷ Silica particles 20.0000 Cross-linked 10.0000 0.100010.0000 10.0000 siloxane particles²⁸ total 100.0000 100.0000 100.0000100.0000 100.0000 100.0000 % Aqueous phase 0.2857 0.2857 0.2857 0.28570.2857 0.2857 % Hydrophobic 99.7143 99.7143 99.7143 99.7143 99.714399.7143 phase % Filler 50.0000 20.0000 10.0000 0.1000 10.0000 10.0000 %H₂O₂ in total 0.099995 0.099995 0.099995 0.099995 0.099995 0.099995compos. RATIO* 350.02 350.02 350.02 350.02 350.02 350.02 *RATIO of theconcentration in weight percent of H₂O₂ present in the aqueous phase tothe concentration in weight percent of H₂O₂ present in the overallcomposition ²²ultra Cosmetic Grade from Solvay, Houston, Texas ²³G-2191Grade from Sonneborn LLC., Parsippany, NJ ²⁴Kaydol grade from SonnebornLLC., Parsippany, NJ ²⁵400 Grade from Baker-Hughes, Houston, TXdissolved into the mineral oil at 95 C. ²⁶W835 Grade from SonnebornLLC., Parsippany, NJ dissolved into the mineral oil at 95° C. ²⁷400Grade from Baker-Hughes, Houston, TX, added into the multi-phase oralcomposition below its melt point such that it is present as particulatefiller ²⁸Tospearl from Momentive Inc. added into the multi-phase oralcomposition such that it is present as particulate filler

FORMULATION COMPARATIVE EXAMPLES Formulation Comparative Examples I

Formulation Comparative Examples I can be made using any suitableprocedure disclosed above or in EP 1 696 866 B1. These examplesillustrate compositions that 1) have H2O2 levels much higher than 0.1%of the overall composition, and 2) have ratios of the concentration inweight percent of H₂O₂ present in the aqueous phase to the concentrationin weight percent of H₂O₂ present in the overall composition lower thanranges preferred according to the present invention.

Formulation Comparative Examples I A B C D (Wt %) (Wt %) (Wt %) (Wt %)35% aqueous sol. 17.00 1.43 17.00 17.00 H₂O₂ ²⁹ Mineral oil³⁰ 77.9093.33 73.90 Aerosol OT³¹ 1.00 1.00 1.00 Polysorbate 80³² 1.00 Silica4.00 Water 4.10 4.24 4.10 4.10 EDTA 0.03 Olive Oil 77.88 total 100.0000100.0000 100.0000 100.0000 % H₂O₂ in total 5.95 0.50 5.95 5.05 compos.RATIO* 4.74 17.64 4.74 4.52 *RATIO of the concentration in weightpercent of H₂O₂ present in the aqueous phase to the concentration inweight percent of H₂O₂ present in the overall composition ²⁹ ultraCosmetic Grade from Solvay, Houston, Texas ³⁰Kaydol grade from SonnebornLLC., Parsippany, NJ ³¹sodium dioctyl sulfosuccinate, from CytecIndustries Inc. NJ. ³²ethoxylated sorbitan monooleate, from SpectrumChemical MfG group ³³ from Calumet Lubricants ³⁴Cetearyl Alcohol andCeteareth-20, from Lipo Chemical.

Formulation Comparative Examples II

Formulation Comparative Examples II can be made using any suitableprocedure disclosed above or in EP 1 696 866 B1. These examplesillustrate compositions that 1) have H2O2 levels much higher than 0.1%of the overall composition, and 2) have ratios of the concentration inweight percent of H₂O₂ present in the aqueous phase to the concentrationin weight percent of H₂O₂ present in the overall composition lower thanranges preferred according to the present invention.

Formulation Comparative Examples II A B C D (Wt %) (Wt %) (Wt %) (Wt %)35% aqueous sol. 17.00 6.00 17.00 17.00 H₂O₂ ³⁵ Mineral oil³⁶ 74.0083.00 63.00 Aerosol OT³⁷ 1.00 1.00 1.00 Polysorbate 80³⁸ 1.00 Silica4.00 Water 8.00 10.00 15.00 10.00 EDTA 0.03 Olive Oil 71.98 total100.0000 100.0000 100.0000 100.0000 % H₂O₂ in total 5.95 2.10 5.95 5.95compos. RATIO* 4.00 6.25 3.13 3.57 *RATIO of the concentration in weightpercent of H₂O₂ present in the aqueous phase to the concentration inweight percent of H₂O₂ present in the overall composition ³⁵ ultraCosmetic Grade from Solvay, Houston, Texas ³⁶Kaydol grade from SonnebornLLC., Parsippany, NJ ³⁷sodium dioctyl sulfosuccinate, from CytecIndustries Inc. NJ. ³⁸ethoxylated sorbitan monooleate, from SpectrumChemical MfG group

The ratio of the concentration in weight percent of bleaching agentpresent in the aqueous phase to the concentration in weight percent ofbleaching agent present in the overall composition of the Formulationcomparative examples I and II range from a minimum of 3.13 to a maximumof 17.64, while the ratio ranges from about 50 to about 34483 inexamples I, II, and III, and Formulation examples I, II, III, IV, and Vabove. Specifically, the ratio of the concentration in weight percent ofbleaching agent present in the aqueous phase to the concentration inweight percent of bleaching agent present in the overall composition ofthe Formulation comparative examples I and II has a maximum value of17.64 while the ratio for examples I, II, and III, and Formulationexamples I, II, III, IV, and V above has a minimum of about 50.

Methods of Using the Compositions and/or Delivery Systems

The present invention can be applied to the teeth of a consumer in thedental office by a dental professional, or can be used at home by theconsumer. Generally, the recommended treatment period is, a sufficientperiod of time to achieve whitening.

In practicing the present invention, the user applies the compositionherein that contains the bleaching agent to obtain the desired effect,such as, whitening, to one or more teeth. The composition can be appliedwith a paint-on device, a syringe or unit dose syringe, squeezable tube,a brush, a pen or brush tip applicator, a doe's foot applicator, swab,lip gloss applicator, strip that is removed after application, tray thatis removed after application, or the like, or even with the fingers. Thecomposition can also be combined with a delivery carrier, such as astrip of material, a dental tray, or a sponge material, and thereafterapplied to the teeth. In certain embodiments, the compositions ordelivery systems herein are almost unnoticeable when applied to theteeth. After a desired period of time has elapsed, any residualcomposition may be easily removed by wiping, brushing or rinsing theoral surface.

In general, it is not necessary to prepare the teeth before applying thepresent composition. For example, the user may choose to brush the teethor rinse the mouth before applying the compositions of the presentinvention, but the surfaces of the oral cavity are neither required tobe clean, nor to be dried nor to be excessively wet with saliva or waterbefore the application. However, it is believed that adhesion to thetooth enamel surfaces will be improved if the teeth are dry prior toapplication.

Dental tray appliances may be used as follows. The patient or dentalprofessional dispenses the present composition into a soft or rigiddental appliance and then the participant places the appliance over theparticipant's dental arch (or fits the device around his or her teeth tokeep the tray in position). Generally, the recommended treatment periodis a sufficient period of time to achieve whitening as disclosed above.At the end of the treatment period, the dental appliance is removed,cleaned with water to remove any remaining composition, and then storeduntil the next application.

The above-described compositions and delivery systems may be combined ina kit which comprises: 1. present composition and 2. instructions foruse; or which comprises: 1. present composition, 2. instructions foruse, and 3. a delivery carrier. In addition, if the tooth shall beradiated by electromagnetic radiation, the kit may further comprise anelectromagnetic radiation source of the appropriate wavelength andinstruction for use, so that the kit can be used by consumers in aconvenient manner

Optional Electromagnetic Radiation Treatment

The multi-phase oral composition as disclosed herein may be used towhiten teeth and/or removing stain from tooth surfaces. In addition, thebleaching efficacy may be further increased by directing electromagneticradiation of a suitable wavelength toward at least one tooth. A devicesuitable to provide such electromagnetic radiation is shown in FIG. 7. Asuitable wavelength may be every wavelength, which corresponds to amaximum absorption band of the tooth and/or the tooth stain to bebleached. For example, the multi-phase oral composition may be radiatedwith an electromagnetic radiation with one or more wavelengths in therange of from about 200 nm to about 1200 nm. The electromagneticradiation may be directed toward at least one tooth. In addition, morethan one tooth may be irradiated. In particular, the electromagneticradiation may have a peak intensity at a wavelength in the range of fromabout 400, 405, 410, 415, 420, 425, 430, 435, 440, or 445, 446 nm toabout 450, 455, 460, 465, 470, 475, 480, 481, 485, 490, 495, or 500 nmor any other numerical range, which is narrower and which falls withinsuch broader numerical range, as if such narrower numerical ranges wereall expressly written herein. In certain embodiments, theelectromagnetic radiation has a peak intensity at a wavelength in therange of from about 425 nm to about 475 nm, from about 445 nm to about465 nm, or wherein the peak intensity wavelength of the electromagneticradiation is similar to the wavelength at which the stain absorbs themost electromagnetic radiation. Electromagnetic radiation may bedirected toward at least one tooth for partial or whole wearing time ofthe composition; or after the composition has been removed from thetooth. Electromagnetic radiation may be applied at least for asufficient period of time for whitening, e.g. for at least about 1minute, for at least about 5 minutes, or for at least about 10 min. Theelectromagnetic radiation may be applied using the procedure disclosedin US 2013/0295525. Preferably the multi-phase oral composition asdisclosed herein is applied to at least one tooth and maintained on theat least one tooth for a first period of time; after the first period oftime electromagnetic radiation is directed toward the at least one toothfor a second period of time, wherein the first period of time has aduration greater than 50%, preferably 80% of a total duration of thefirst and second periods of time; and finally, the multi-phase oralcomposition is removed from the at least one tooth.

Suitable sources of electromagnetic radiation include the sourcedescribed herein in the section titled “Clinical Protocol”.

The multi-phase oral compositions as disclosed herein may be transparentor translucent to electromagnetic radiation with wavelengths from about400 nm to about 500 nm. In certain embodiments, the multi-phase oralcompositions as disclosed herein when applied in a thickness of fromabout 0.0001, 0.001, or 0.01 cm to about 0.01, 0.1, or 0.5 cm thickallow from about 10%, 20%, or 30% to about 40%, 50%, 60%, 70%, 80%, 90%,or 100% of electromagnetic radiation from about 400 nm to about 500 nmto pass through, as measured by a spectrophotometer. In certainembodiments, when a multi-phase oral composition is applied in athickness of about 0.1 cm, from about 80% to about 100% ofelectromagnetic radiation from about 400 nm to about 500 nm passesthrough, as measured by a spectrophotometer. The multi-phase oralcompositions, as disclosed herein, may when applied in an amount fromabout 0.0001, 0.001, or 0.01 grams to about 0.01, 0.1, 1, or 5 grams, ona delivery carrier or tray with a surface area from about 5 cm² to about20 cm², allow from about 10%, 20%, or 30% to about 40%, 50%, 60%, 70%,80%, 90%, or 100% of electromagnetic radiation from about 400 nm toabout 500 nm to pass through.

The electromagnetic radiation impinging on the surface of the tooth orouter surface of the carrier, which may be a strip, in the wavelengthrange from about 400 to about 500 nm may range in intensity from about5, 10, 25, 50, 75, or 100 mW/cm2 to about 500, 250, 225, 205, 200, 175,150, 125, 100, 75, 50, 25, 10, or 5 mW/cm2 or any other numerical range,which is narrower and which falls within such broader numerical range,as if such narrower numerical ranges were all expressly written herein.

Procedure to Measure Intensity of Electromagnetic Radiation

The intensity of the electromagnetic radiation can be measured using aspectrometer (USB 2000+ from Ocean Optics) connected to a UV-VIS 200micron fiber-optic cable with a cosine corrector at the tip (OP200-2-UV-VIS from Ocean Optics). The spectrometer is connected to acomputer running the spectrometer software (Oceanview 1.3.4 from OceanOptics). The tip of the fiber-optic cable is held pointing toward thelight source at the location where the light intensity is to bemeasured. The photons collected at the detector surface are guided viathe fiber-optic cable to the charge-coupled device in the spectrometer(CCD). The CCD counts photons arriving to the CCD during apre-determined time period at each wavelength from 200 nm to 1100 nm,and uses a software algorithm to convert these photon counts to spectralirradiance (mW/cm²/nm). The spectral irradiance is integrated from 200nm to 1100 nm by the software to yield the Absolute Irradiance (mW/cm²),which is the intensity of electromagnetic radiation from 200 nm to 1100nm. The spectral irradiance is integrated from 400 nm to 500 nm by thesoftware to yield the Absolute Irradiance (mW/cm²), which is theintensity of electromagnetic radiation from 400 nm to 500 nm.

For consumer convenience, the multi-phase oral composition as disclosedherein may be provided as a Kit comprising the bleaching composition asdisclosed herein, a delivery carrier for easier application, anelectromagnetic radiation source emitting electromagnetic radiation in asuitable wavelength, and instructions for use.

The compositions of this invention are useful for both human and otheranimals (e.g. pets, zoo, or domestic animals) applications.

EXAMPLES

The following non-limiting examples further describe preferredembodiments within the scope of the present invention. Many variationsof these examples are possible without departing from the scope of theinvention. All examples were performed at room temperature (RT) andatmospheric pressure unless stated otherwise.

These multi-phase oral compositions were made as described previously orbelow.

Specifically, 500 gram batches of Example-I-A, and B, Example-II-A, B,and C, Comparative Example-I, and Example-III A, B, C, and D were madeby weighing the aqueous solution of hydrogen peroxide (H2O2) andpetrolatum into a Speedmixer container (“Max 300 Long Cup Translucent”,item number 501 218t from Flacktek Inc., Landrum, S.C.), and mixing in aSpeedmixer at 800 RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950RPM for 2 minutes. The walls of the container were then scraped downwith a plastic spatula, and the contents were mixed a second time at 800RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2 minutes.The walls of the container were then scraped down with a plasticspatula, and the contents were mixed a third time at 800 RPM for 5seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2 minutes.

Also, a 500 gram batch of Example-III E was made by first weighing thepolyethylene and mineral oil into a Speedmixer container (“Max 300 LongCup Translucent”, item number 501 218t from Flacktek Inc., Landrum,S.C.), heating it in an oven set at 95° C. for about 3 hours, mixingwith a spatula for about 30 seconds, followed by mixing in a Speedmixerat 800 RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2minutes, and cooling overnight at room temperature. Next, the aqueoussolution of H2O2 was added and mixed in a Speedmixer at 800 RPM for 5seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2 minutes. The wallsof the container were then scraped down with a plastic spatula, and thecontents were mixed a second time at 800 RPM for 5 seconds, 1200 RPM for5 seconds, and 1950 RPM for 2 minutes. The walls of the container werethen scraped down with a plastic spatula, and the contents were mixed athird time at 800 RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950RPM for 2 minutes.

Also, a 500 gram batch of Example-III F was made by first weighing themicrocrystalline wax and mineral oil into a Speedmixer container (“Max300 Long Cup Translucent”, item number 501 218t from Flacktek Inc.,Landrum, S.C.), heating it in an oven set at 95° C. for about 3 hours,mixing with a spatula for about 30 seconds, followed by mixing in aSpeedmixer at 800 RPM for 30 seconds, and cooling overnight at roomtemperature. Next, the aqueous solution of H2O2 was added and mixed in aSpeedmixer at 800 RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950RPM for 2 minutes. The walls of the container were then scraped downwith a plastic spatula, and the contents were mixed a second time at 800RPM for 5 seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2 minutes.The walls of the container were then scraped down with a plasticspatula, and the contents were mixed a third time at 800 RPM for 5seconds, 1200 RPM for 5 seconds, and 1950 RPM for 2 minutes.

Also, a batch of Example IV-A was made as follows: 242.6 g Petrolatumand 7.2 g of 35% aqueous Hydrogen Peroxide were added into a Max 300Long Speedmixer container (Flacktek Inc., Landrum, S.C.) and mixed in aSpeedMixer DAC 400 FVZ (Flacktek Inc., Landrum, S.C.) for 30 seconds at1600 rev/min. The mixture was transferred to an empty 12.8 oz CaulkCartridge (McMaster Carr, Robbinsville, N.J.) and stored in arefrigerator until the measured product temperature was 9° C. The CaulkCartridge was inserted into a Pneumatic Caulk Gun (McMaster Carr,Robbinsville, N.J.), and connected to the inlet of a Microfluidizermodel M-110Y (Microfluidics, Westwood, Mass. 02090). The outlet pipingof the Microfluidizer was arranged such that the product passed throughonly a F20Y Interaction Chamber and several cm of piping before andafter. The inlet pressure to the Microfluidizer was adjusted to 42 psig,and the inlet pressure to the Caulk Cartridge was adjusted to 94 psig.The final product was collected in a plastic container.

Also, a batch of Example IV-B was made as follows: 228.8 g Petrolatumand 21.6 g of 35% aqueous Hydrogen Peroxide were added into a Max 300Long Speedmixer container (Flacktek Inc., Landrum, S.C.) and mixed in aSpeedMixer DAC 400 FVZ (Flacktek Inc., Landrum, S.C.) for 30 seconds at1600 rev/min. The mixture was transferred to an empty 12.8oz CaulkCartridge (McMaster Carr, Robbinsville, N.J.) and stored in arefrigerator until the measured product temperature was 8° C. The CaulkCartridge was inserted into a Pneumatic Caulk Gun (McMaster Carr,Robbinsville, N.J.), and connected to the inlet of a Microfluidizermodel M-110Y (Microfluidics, Westwood, Mass. 02090). The outlet pipingof the Microfluidizer was arranged such that the product passed throughonly a F20Y Interaction Chamber and several cm of piping before andafter. The inlet pressure to the Microfluidizer was adjusted to 42 psig,and the inlet pressure to the Caulk Cartridge was adjusted to 94 psig.The final product was collected in a plastic container.

Example I

Multi-phase oral compositions of Example I-A, and B were made using theprocedure described above and formulated with a 35% aqueous solution ofhydrogen peroxide. The following parameters were measured on Example-I-Busing the procedures specified herein: a) two-dimensional density ofdroplets of aqueous phase of the multi-phase oral composition with across-sectional area larger than 10000 square microns per squarecentimeter of the two-dimensional plane; b) Standard deviation of theperoxide concentration of the multi-phase oral composition smeared onperoxide test strips; c) Mean peroxide concentration of the multi-phaseoral composition smeared onto peroxide test strips.

Example I A B (Wt %) (Wt %) 35% aqueous solution H₂O₂ ¹ 0.2857 2.857Petrolatum² 99.7143 97.143 total 100.00 100.00 % H₂O₂ in total oralcompos. 0.099995 0.99995 RATIO* 350.02 35.002 Two-dimensional density ofdroplets of aqueous 10.3 phase with a cross-sectional area larger than10000 square microns per square centimeter of the two- dimensional planemeasured using the procedure specified herein Standard deviation of theperoxide concentration of 50.17 the multi-phase oral composition smearedon peroxide test strips measured using the procedure specified hereinMean peroxide concentration of the multi-phase oral 47.55 compositionsmeared onto peroxide test strips measured using the procedure specifiedherein Ratio of the mean peroxide concentration of the 0.95 multi-phaseoral composition smeared onto peroxide test strips measured using theprocedure specified herein to the standard deviation of the peroxideconcentration of the multi-phase oral composition smeared on peroxidetest strips measured using the procedure specified herein *RATIO of theconcentration in weight percent of H₂O₂ present in the aqueous phase tothe concentration in weight percent of H₂O₂ present in the overallcomposition ¹ultra Cosmetic Grade from Solvay, Houston, Texas ²G-2191Grade from Sonneborn, LLC., Parsippany, NJ

Example II

Multi-phase oral composition of Example II-A was made using theprocedure described above and formulated with a 17.5% aqueous solutionof hydrogen peroxide. Multi-phase oral compositions of Example II-B, andC were made using the procedure described above and formulated with a 5%aqueous solution of hydrogen peroxide.

Example II A B C (Wt %) (Wt %) (Wt %) 17.5% aqueous 0.5714 0.0000 0.0000sol. H₂O₂ ³ 5% aqueous 0.0000 1.0000 2.0000 sol. H₂O₂ ³ Petrolatum⁴99.4286 99.0000 98.0000 total 100.0 100.0 100.0 % H₂O₂ in 0.0999950.0500 0.1000 total compos. RATIO* 175.01 100.00 50.00 *RATIO of theconcentration in weight percent of H₂O₂ present in the aqueous phase tothe concentration in weight percent of H₂O₂ present in the overallcomposition ³ultra Cosmetic Grade from Solvay (Houston, Texas) dilutedwith water ⁴G-2191 Grade from Sonneborn, LLC., Parsippany, NJ

Example III

Multi-phase oral compositions of Examples III were made using theprocedure described above and formulated with 1) a 35% aqueous solutionof hydrogen peroxide of different chemical grades as well as 2)different materials used as the hydrophobic phase.

Example III A B C D E F (Wt %) (Wt %) (Wt %) (Wt %) (Wt %) (Wt %) 35%aqueous 0.2857 0.2857 0.2857 0.2857 sol. H₂O₂ ⁵ 35% aqueous 0.2857 sol.H₂O₂ ⁶ 35% aqueous 0.2857 sol. H₂O₂ ⁷ Petrolatum⁸ 99.7143 99.7143Petrolatum⁹ 99.7143 Petrolatum¹⁰ 99.7143 Mineral oil¹¹ 79.7143 49.7143Polyethylene¹² 20.00 Microcrystalline 50.00 Wax¹³ total 100.0 100.0100.0 100.0 100.0 100.0 % H₂O₂ in total 0.099995 0.099995 0.0999950.099995 0.099995 0.099995 compos. RATIO* 350.02 350.02 350.02 350.02350.02 350.02 *RATIO of the concentration in weight percent of H₂O₂present in the aqueous phase to the concentration in weight percent ofH₂O₂ present in the overall composition ⁵ultra Cosmetic Grade fromSolvay, Houston, Texas ⁶Technical Grade from Solvay, Houston, Texas⁷Technical grade from Solvay Stabilized with added Stabilizers ⁸G-2191Grade from Sonneborn, LLC., Parsippany, NJ ⁹G-1958 Grade from Sonneborn,LLC., Parsippany, NJ ¹⁰G-2218 Grade from Sonneborn, LLC., Parsippany, NJ¹¹Kaydol grade from Sonneborn, LLC., Parsippany, NJ ¹²400 Grade fromBaker-Hughes, Houston, TX, dissolved into the mineral oil at about 95 C.¹³W835 Grade from Sonneborn, LLC., Parsippany, NJ, dissolved into themineral oil at about 95° C.

Example IV

Multi-phase oral compositions of Example IV-A, and B were made using theprocedure described above and formulated with a 35% aqueous solution ofhydrogen peroxide. The following parameters were measured on ExamplesIV-A, and IV-B using the procedures specified herein: a) two-dimensionaldensity of droplets of aqueous phase of the multiphase oral compositionwith a cross-sectional area larger than 10000 square microns per squarecentimeter of the two-dimensional plane; b) Standard deviation of theperoxide concentration of the multi-phase oral composition smeared onperoxide test strips; c) Mean peroxide concentration of the multi-phaseoral composition smeared onto peroxide test strips.

Example IV A B (Wt %) (Wt %) 35% aqueous solution H₂O₂ ¹⁴ 2.857 8.571Petrolatum¹⁵ 99.7143 91.429 total 100.00 100.00 % H₂O₂ in total oralcompos. 0.99995 2.99985 RATIO* 35.02 11.67 “Two-dimensional density ofdroplets” of aqueous phase 0.1 2.95 with a cross-sectional area largerthan 10000 square microns per square centimeter of the two-dimensionalplane measured using the procedure specified herein Standard deviationof the peroxide concentration of the 5.15 12.39 multi-phase oralcomposition smeared onto peroxide test strips measured using theprocedure specified herein Mean peroxide concentration of themulti-phase oral 14.87 49.22 composition smeared onto peroxide teststrips measured using the procedure specified herein Ratio of the meanperoxide concentration of the multi- 2.89 3.97 phase oral compositionsmeared onto peroxide test strips measured using the procedure specifiedherein to the standard deviation of the peroxide concentration of themulti-phase oral composition smeared on peroxide test strips measuredusing the procedure specified herein *RATIO of the concentration inweight percent of H₂O₂ present in the aqueous phase to the concentrationin weight percent of H₂O₂ present in the overall composition ¹⁴ultraCosmetic Grade from Solvay, Houston, Texas ¹⁵G-2218 Grade fromSonneborn, LLC., Parsippany, NJ

Comparative Examples

All examples were performed at room temperature (RT) and atmosphericpressure unless stated otherwise.

Comparative Example I

Comparative Example I was made using the procedure described above andformulated with no bleaching agent.

Comparative Example I (Wt %) Petrolatum¹⁴ 100.0000 total 100.0000 % H₂O₂in total 0.0000 oral compos. ¹⁴G-2191 Grade from Sonneborn, LLC.,Parsippany, NJ

Bleaching Efficacy of Example-IA Versus Comparative Example-I

The bleaching efficacy of Example-IA and Comparative Example-I weremeasured per the clinical protocol disclosed herein. Specifically, thiswas a randomized, single-center, two-treatment, parallel group, clinicalstudy conducted on 39 adults who had never had a professional,over-the-counter or investigational tooth bleaching treatment. Allparticipants were at least 18 years old, had all four measurablemaxillary incisors, and had no self-reported tooth sensitivity.Participants were randomized to study treatments based on L* and b*color values and age. Participants were assigned to one of two treatmentgroups:

Example-IA (22 participants, mean L* of 74.1 and mean b* of 15.6) or

Comparative Example-I (17 participants, mean L* of 74.2 and mean b* of15.2)

The maxillary anterior teeth of the participants were treated with theoral composition they were assigned for 60 minutes once daily using astrip of polyethylene as a delivery carrier. The polyethylene stripswere 66 mm×15 mm in size and 0.0178 mm thick. 0.6 grams to 0.8 grams ofthe oral compositions were applied across each strip of polyethyleneprior to applying to the maxillary anterior teeth.

Distribution of the assigned maxillary strips and all applications weresupervised by a clinical site staff. For each treatment, participantswore a strip with the oral composition they were assigned for a total of60 minutes. After 50 minutes of each strip wear, a trained hygienistapplied electromagnetic radiation toward the facial surfaces of themaxillary anterior teeth for 10 minutes. The electromagnetic radiationwas directed toward the teeth through the strip and through the oralcomposition. The electromagnetic radiation was delivered using thesource of electromagnetic radiation described herein in the sectiontitled “Clinical Protocol”. The intensity of the electromagneticradiation from 400 nm to 500 nm measured at the central axis of eachcone of electromagnetic radiation exiting at the exit surface of thetransparent window through which the electromagnetic radiation passestoward the maxillary anterior teeth was measured to be from about 175mW/cm² to about 225 mW/cm², as measured by the procedure disclosedherein.

Digital images were collected at Baseline, and the day after the 3^(rd),7^(th), 10^(th), and 14^(th) treatments.

The group using Example-IA demonstrated a statistically significant(p<0.0001), incremental reduction in yellowness (−Δb*) at all testedtime-points relative to Baseline; in addition, increase in lightness(ΔL*) was observed in this group the day after seven, ten, and fourteentreatments (p<0.001).

The group using comparative Example-I did not differ from Baselinevalues after three, seven, and ten applications, and showed a smallstatistically significant (p=0.0007) decrease in yellowness (−Δb*) afterfourteen treatments; no changes in lightness (ΔL*) were detected.

Furthermore, the group on Example-IA demonstrated a larger decrease inyellowness −Δb*) compared to the group on comparative Example-I at alltested time-points.

Table I shows the results in detail:

Comparative Example-I Example-IA (0.099995% (0% H₂O₂ delivered on %Improvement H₂O₂ delivered on a strip and same strip and used deliveredby used with an electromagnetic with same electromagnetic Example-IAover Mean change in radiation source described radiation sourcedescribed Comparative yellowness from herein in the section titledherein in the section titled Example-I under baseline (Δb*) “ClinicalProtocol”) “Clinical Protocol”) same conditions After 3 treatments−0.607 0.073 >800% (Day 4) After 7 treatments −1.45 0.005 >800% (Day 8)After 10 treatments −1.70 −0.191 >800% (Day 11) After 14 treatments−1.95 −0.408 >400% (Day 15)

These results clearly demonstrate the surprisingly high efficacy ofExample-IA (delivered on a strip and used with electromagnetic radiationas disclosed herein) even though it has less than 0.1% H2O2.

The ratio of bleaching efficacy of Example-IA (delivered on a strip andused with electromagnetic radiation as disclosed herein), as measuredper the clinical protocol as disclosed herein, and calculated as −Δb* tothe weight percent of bleaching agent present in the overall oralcomposition was 6.07, 14.5, 17.0, and 19.5 after 3, 7, 10, and 14treatments respectively.

These results also clearly demonstrate the surprisingly high efficacy ofExample-IA (delivered on a strip and used with electromagnetic radiationas disclosed herein) relative to the comparative Example-I (delivered onsame strip and used with the same electromagnetic radiation source).

FIG. 7 shows images of example teeth treated with the bleachingmulti-phase oral composition of Example IA. RGB images were converted toblack-and-white images. Images were taken before and after 14 treatmentswith multi-phase oral composition of Example IA. Three teeth were shown,wherein the left side of the tooth shows its baseline visual appearanceand the right side of the tooth shows its visual appearance after 14treatments. It can be clearly seen that the treatment with Example IAmulti-phase oral composition visibly whitens the tooth surface. Allthree teeth appear whiter on the right side compared to the left side.

It is also surprising that none of the study participants reportedtooth-sensitivity despite experiencing the high efficacy of Example-IA(delivered on a strip and used with an electromagnetic radiation sourceas disclosed herein).

Comparative Example II

Comparative example II is a commercially available Crest Whitestripstooth whitening strip product with 5.25% H2O2 (from Procter & Gamble,Cincinnati, Ohio, USA). This is an aqueous gel containing 5.25% hydrogenperoxide (H₂O₂); and since it is an aqueous gel, the ratio of theconcentration in weight percent of H2O2 present in the aqueous phase tothe concentration in weight percent of H2O2 present in the overallcomposition is 1.

Bleaching Efficacy of Comparative Example II (Aqueous Gel with 5.25%H2O2)

The bleaching efficacy of a second comparative composition (ComparativeExample II—Crest Whitestrips tooth whitening strip product with 5.25%H2O2) containing a final concentration of 5.25% H₂O₂ in an aqueous gelwas measured in a clinical study. Specifically, the study forComparative Example II was a controlled, single-center clinical trial.The target population was adult participants with no previous history oftooth whitening. Participants were treated with the above comparativeaqueous gel with 5.25% H₂O₂ (Comparative Example II) delivered on astrip of polyethylene. The group (20 participants, mean L* of 72.8 andmean b* of 16.4) wore the strip for 60 minutes once daily for 14 days.

Digital images were obtained at Baseline, and the day after the 7^(th)and 14^(th) treatments. The results of the group who wore thecomparative Example II (aqueous gel with 5.25% H₂O₂) delivered on astrip for 60 minutes (same length of time as Example-IA in the clinicaldescribed previously) are shown in the table below.

Table II shows the results in detail:

Example-IA (composition of invention containing about 0.1% H2O2)(delivered on a strip for 60 minutes, and used with an electromagneticComparative Example II Mean change in radiation source described(aqueous gel containing about yellowness from herein in the sectiontitled 5.25% H2O2) (delivered on a baseline (Δb*) “Clinical Protocol”)strip for 60 minutes) After 7 treatments −1.45 −0.985 (Day 8) After 14treatments −1.95 −1.43 (Day 15)

After 7 treatments, the comparative Example II (aqueous gel with 5.25%H₂O₂, delivered on a strip for 60 minutes) produced a mean change inyellowness of −0.985 while Example-IA (also delivered on a strip, andused with an electromagnetic radiation source) delivered a mean changein yellowness of −1.45 even though it had approximately 5250% lowerconcentration of H₂O₂ vs. the aqueous gel (0.1% H₂O₂ Vs. 5.25% H₂O₂)used in Comparative Example II. Similarly, after 14 treatments, thecomparative Example II produced a mean change in yellowness of −1.43while Example-IA delivered a mean change in yellowness of −1.95 eventhough it had approximately 5250% lower concentration of H₂O₂ Vs. theaqueous gel (0.1% H₂O₂ vs. 5.25% H₂O₂). It is worth noting from table I,that Comparative Example I which had the same electromagnetic radiationsource disclosed herein but with 0.0% H₂O₂ delivered a mean change inyellowness of only 0.005 and −0.408 after 7 and 14 treatmentsrespectively. These results also clearly demonstrate the surprisinglyhigh efficacy of Example-IA (delivered on a strip and used with anelectromagnetic radiation source as disclosed herein) even though it hasapproximately 5250% lower concentration of H₂O₂ Vs. the comparativeaqueous gel (0.1% H₂O₂ Vs. 5.25% H₂O₂) used in Comparative Example II.

Also, it is worth noting that the ratio of the concentration in weightpercent of bleaching agent present in the aqueous phase to theconcentration in weight percent of bleaching agent present in theoverall composition of the comparative example II is 1, while example IAhas a ratio of 350.02.

The ratio of bleaching efficacy of Comparative Example II, calculated as−Δb* to the weight percent of bleaching agent present in the overalloral composition was 0.19 and 0.27, after 7 and 14 treatmentsrespectively. This is lower than the ratio of bleaching efficacy ofExample-IA (delivered on a strip and used with an electromagneticradiation source as disclosed herein), calculated as −Δb* to the weightpercent of bleaching agent present in the overall oral composition whichwas measured to be 14.5 and 19.5, after 7 and 14 treatmentsrespectively.

Bleaching Efficacy of Example-IB

The bleaching efficacy of Example-IB was measured per the clinicalprotocol disclosed herein. Specifically, this was a single-center,single-treatment clinical study with 8 adults who had never had aprofessional, over-the-counter or investigational tooth bleachingtreatment. All participants were at least 18 years old, had all fourmeasurable maxillary incisors, and had no self-reported toothsensitivity. Participants were assigned to the following treatmentgroup:

Example-IB (8 participants, mean L* of 73.248 and mean b* of 16.368)

The maxillary anterior teeth of the participants were treated with themulti-phase oral composition Example-IB for 60 minutes once daily usinga strip of polyethylene as a delivery carrier for three days. Thepolyethylene strips were 66 mm×15 mm in size and 0.0178 mm thick. 0.6grams to 0.8 grams of the multi-phase oral composition was appliedacross each strip of polyethylene prior to applying to the maxillaryanterior teeth.

Distribution of the maxillary strips and all applications were performedby a clinical site staff. Participants wore a strip with the multi-phaseoral composition for a total of 60 minutes per treatment for three days.After 50 minutes of each strip wear, a trained hygienist appliedelectromagnetic radiation toward the facial surfaces of the maxillaryanterior teeth for 10 minutes. The electromagnetic radiation wasdirected toward the teeth through the strip and through the multi-phaseoral composition. The electromagnetic radiation was delivered using thesource of electromagnetic radiation described herein in the sectiontitled “Clinical Protocol”. The intensity of the electromagneticradiation from 400 nm to 500 nm measured at the central axis of eachcone of electromagnetic radiation exiting at the exit surface of thetransparent window through which the electromagnetic radiation passestoward the maxillary anterior teeth was measured to be from about 175mW/cm² to about 225 mW/cm², as measured by the procedure disclosedherein.

Digital images were collected before the strips were applied on Day 1(Baseline), Day 2, and Day 3; and after the strips were removed on Day1, Day 2, and Day 3.

The participants demonstrated a statistically significant (p<0.0001)reduction in yellowness (−Δb*) at all tested time-points relative toBaseline.

Table III shows the results in detail:

Example-IB (0.99995% H₂O₂ delivered on a strip and used with anelectromagnetic radiation source described herein in the Mean change inyellowness from baseline (Δb*) section titled “Clinical Protocol”) After1 treatment −1.604 (Day 1) After 2 treatments −1.996 (Day 2) After 3treatments −2.931 (Day 3) % of participants who reported or were 37.5observed to have oral irritation that was possibly or probably relatedto the product % of participants who reported tooth sensitivity 12.5that was possibly or probably related to the product % of participantswho reported or were 50 observed to have oral irritation or toothsensitivity that was possibly or probably related to the product Ratioof bleaching efficacy of the present 7.816 invention, as measured perthe clinical protocol as disclosed herein, and calculated as −Δb* after3 treatments to the fraction of participants who reported oralirritation or were observed to have oral irritation that was possibly orprobably attributed to the composition tested Ratio of bleachingefficacy of the present 23.448 invention, as measured per the clinicalprotocol as disclosed herein, and calculated as −Δb* after 3 treatmentsto the fraction of participants who reported tooth sensitivity that waspossibly or probably attributed to the composition tested Ratio ofbleaching efficacy of the present 5.862 invention, as measured per theclinical protocol as disclosed herein, and calculated as −Δb* after 3treatments to the fraction of participants who reported toothsensitivity or reported oral irritation or were observed to have oralirritation that was possibly or probably attributed to the compositiontested

These results clearly demonstrate the surprisingly high efficacy ofExample-IB (delivered on a strip and used with electromagneticradiation, as disclosed herein) even though it has less than 1% H₂O₂.This is even more surprising since this high efficacy was deliveredafter just 1, 2 or 3 treatments. Furthermore, despite the high efficacy,surprisingly only 12.5% of the participants reported tooth sensitivityand even this was characterized as mild.

It is worth noting from table II that even after 7 treatments,comparative Example II (aqueous gel with 5.25% H₂O₂, delivered on astrip for 60 minutes) produced a mean change in yellowness of only−0.985 while Example-IB (also delivered on a strip, and used with anelectromagnetic radiation source) delivered a mean change in yellownessof −2.931 after just 3 treatments even though it had approximately 525%lower concentration of H₂O₂ vs. the aqueous gel (0.99995% H₂O₂ Vs. 5.25%H₂O₂) used in Comparative Example II. It is also worth noting from tableI that even after 7 treatments, comparative Example I which had the sameelectromagnetic radiation source disclosed herein, but with 0.0% H₂O₂delivered a mean change in yellowness of only 0.005 while Example-IB(also delivered on a strip, and used with the same electromagneticradiation source) delivered a mean change in yellowness of −2.931 afterjust 3 treatments. This further highlights the surprisingly highefficacy of Example-IB.

Bleaching Efficacy of Examples IV-A and IV-B

The bleaching efficacy of Examples IV-A and IV-B were measured per theclinical protocol disclosed herein. Specifically, this was a randomized,single-center, two-treatment, parallel group, clinical study with 23adults who had never had a professional, over-the-counter orinvestigational tooth bleaching treatment. All participants were atleast 18 years old, had all four measurable maxillary incisors, and hadno self-reported tooth sensitivity. Participants were randomized tostudy treatments based on L* and b* color values and age. Participantswere assigned to one of two treatment groups:

Example-IV-A (11 participants, mean L* of 70.342 and mean b* of 16.669)or

Example-IV-B (12 participants, mean L* 72.146 and mean b* of 17.170)

The maxillary anterior teeth of the participants were treated with theassigned multi-phase oral composition for 60 minutes once daily using astrip of polyethylene as a delivery carrier for three days. Thepolyethylene strips were 66 mm×15 mm in size and 0.0178 mm thick. 0.6grams to 0.8 grams of the multi-phase oral composition was appliedacross each strip of polyethylene prior to applying to the maxillaryanterior teeth.

Distribution of the maxillary strips and all applications were performedby a clinical site staff. Participants wore the strip with themulti-phase oral composition for a total of 60 minutes each day forthree days. After 50 minutes of each strip wear, a trained hygienistapplied electromagnetic radiation toward the facial surfaces of themaxillary anterior teeth for 10 minutes. The electromagnetic radiationwas directed toward the teeth through the strip and through themulti-phase oral composition. The electromagnetic radiation wasdelivered using the source of electromagnetic radiation described hereinin the section titled “Clinical Protocol”. The intensity of theelectromagnetic radiation from 400 nm to 500 nm measured at the centralaxis of each cone of electromagnetic radiation exiting at the exitsurface of the transparent window, through which the electromagneticradiation passes toward the maxillary anterior teeth was measured to befrom about 175 mW/cm² to about 225 mW/cm² as measured by the proceduredisclosed herein.

Digital images were collected before the strips were applied on Day 1(Baseline), Day 2, and Day 3; and after the strips were removed on Day1, Day 2, and Day 3.

The participants demonstrated a statistically significant (p<0.0001)reduction in yellowness (−Δb*) at all tested time-points relative toBaseline.

Table IV shows the results in detail:

Example-IV-A (0.99995% H₂O₂ Example-IV-B (2.99985% H₂O₂ delivered on astrip and used delivered on a strip and used with an electromagneticwith an electromagnetic radiation source described radiation sourcedescribed herein in the section titled herein in the section titled“Clinical Protocol”) “Clinical Protocol”) Mean change in yellowness from−1.294 −1.778 baseline (Δb*) after 1 treatment (Day 1) Mean change inyellowness from −1.946 −2.286 baseline (Δb*) after 2 treatments (Day 2)Mean change in yellowness from −2.086 −3.204 baseline (Δb*) after 3treatments (Day 3) % of participants who reported or 9.1 16.7 wereobserved to have oral irritation that was possibly or probably relatedto the product % of participants who reported 0 16.7 tooth sensitivitythat was possibly or probably related to the product % of participantswho reported or 9.1 33.3 were observed to have oral irritation or toothsensitivity that was possibly or probably related to the product Ratioof bleaching efficacy of the 22.923 19.186 present invention, asmeasured per the clinical protocol as disclosed herein, and calculatedas −Δb* after 3 treatments to the fraction of participants who reportedoral irritation or were observed to have oral irritation that waspossibly or probably attributed to the composition tested Ratio ofbleaching efficacy of the >100 19.186 present invention, as measured perthe clinical protocol as disclosed herein, and calculated as −Δb* after3 treatments to the fraction of participants who reported toothsensitivity that was possibly or probably attributed to the compositiontested Ratio of bleaching efficacy of the 22.923 9.622 presentinvention, as measured per the clinical protocol as disclosed herein,and calculated as −Δb* after 3 treatments to the fraction ofparticipants who reported sensitivity or reported oral irritation orwere observed to have oral irritation that was possibly or probablyattributed to the composition tested

These results clearly demonstrate the surprisingly high efficacy and lowlevel of oral irritation and tooth sensitivity of Examples-IV-A(delivered on a strip and used with electromagnetic radiation asdisclosed herein). This is even more surprising since this high efficacywas delivered after just 1, 2 or 3 treatments even though it had onlyabout 0.99995% H₂O₂.

As before, it is worth noting from table II that even after 7treatments, comparative Example II (aqueous gel with 5.25% H₂O₂,delivered on a strip for 60 minutes) produced a mean change inyellowness of only −0.985 while Example-IV-A (also delivered on a strip,and used with an electromagnetic radiation source) delivered a meanchange in yellowness of −2.086 after just 3 treatments even though ithad approximately 525% lower concentration of H₂O₂ vs. the aqueous gel(0.99995% H₂O₂ Vs. 5.25% H₂O₂) used in Comparative Example II. It isalso worth noting from Table I that even after 7 treatments comparativeExample I, which had the same electromagnetic radiation source disclosedherein, but with 0.0% H₂O₂ delivered a mean change in yellowness of only0.005 while Example-IV-A (also delivered on a strip, and used with thesame electromagnetic radiation source) delivered a mean change inyellowness of −2.086 after just 3 treatments. This further highlightsthe surprisingly high efficacy of Example-IV-A.

Combining the observation that: 1) Example I-B delivered a mean decreasein yellowness (−Δb*) of 2.931 after three treatments while Example IV-Adelivered a mean decrease in yellowness (−Δb*) of 2.086 after threetreatments with the observation that; 2) the mean peroxide concentrationof the multi-phase oral composition smeared on peroxide test stripsmeasured using the procedure specified herein is also higher for ExampleI-B Vs. IV-A (47.55 Vs. 14.87) despite both examples having the samelevel of H2O2 (about 0.99995%) shows that bleaching efficacy, asmeasured by the mean decrease in yellowness (−Δb*), increases as themean peroxide concentration of the multi-phase oral composition smearedon peroxide test strips measured using the procedure specified hereinincreases.

Furthermore, despite the high efficacy of Example-IV-A, surprisinglyonly 9.1% of the participants reported or were observed to have oralirritation, 0% of the participants reported tooth sensitivity, and only9.1% of the participants were observed to have or to have oralirritation or tooth sensitivity that was possibly or probably related tothe product and even these were characterized as mild.

Combining the observation that: 1) only 9.1% of participants reported orwere observed to have oral irritation and 0% of participants reportedtooth sensitivity when treated with Example IV-A, while 37.5% ofparticipants reported or were observed to have oral irritation and 12.5%of participants reported tooth sensitivity when treated with Example I-Bwith the observation that; 2) the two-dimensional density of droplets ofaqueous phase with a cross-sectional area larger than 10000 squaremicrons per square centimeter of the two-dimensional plane measuredusing the procedure specified herein was also lower for Example IV-A Vs.I-B (0.1 Vs. 10.3) despite both examples having the same level of H2O2(about 0.99995%%) shows that oral irritation and tooth sensitivitydecrease as two-dimensional density of droplets of aqueous phase with across-sectional area larger than 10000 square microns per squarecentimeter of the two-dimensional plane measured using the procedurespecified herein decreases.

Combining the observation that: 1) only 9.1% of participants reported orwere observed to have oral irritation and 0% of participants reportedtooth sensitivity when treated with Example IV-A while 37.5% ofparticipants reported or were observed to have oral irritation and 12.5%of participants reported tooth sensitivity when treated with Example I-Bwith the observation that; 2) the standard deviation of the peroxideconcentration of the multi-phase oral composition smeared on peroxidetest strips measured using the procedure specified herein was also lowerfor Example IV-A Vs. I-B (5.15 Vs. 50.17), despite both examples havingthe same level of H2O2 (about 0.99995%), shows that oral irritation andtooth sensitivity decrease as the standard deviation of the peroxideconcentration of the multi-phase oral composition smeared on peroxidetest strips measured using the procedure specified herein decreases.

Further, combining the observation that: 1) the ratio of the bleachingefficacy to the fraction of participants who reported oral irritation orwere observed to have oral irritation was 22.923 for Example IV-A andonly 7.816 for Example I-B with the observation that 2) the ratio of themean peroxide concentration of the multi-phase oral composition smearedonto peroxide test strips to the standard deviation of the peroxideconcentration of the multi-phase oral composition smeared onto peroxidetest strips was also higher for Example IV-A Vs. Example I-B (2.89 Vs.0.95), even though both examples had the same level of bleaching agent(about 1%), shows that the ratio of the bleaching efficacy to thefraction of participants who reported oral irritation or were observedto have oral irritation decreases as the ratio of the mean peroxideconcentration of the multi-phase oral composition smeared onto peroxidetest strips to the standard deviation of the peroxide concentration ofthe multi-phase oral composition smeared on peroxide test stripsdecreases.

Combining the observation that: 1) the ratio of the bleaching efficacyto the fraction of participants who reported tooth sensitivity was >100for Example IV-A and only 23.448 for Example I-B with the observationthat; 2) the ratio of the mean peroxide concentration of the multi-phaseoral composition smeared onto peroxide test strips to the standarddeviation of the peroxide concentration of the multi-phase oralcomposition smeared on peroxide test strips was also higher for ExampleIV-A Vs. Example I-B (2.89 Vs. 0.95), even though both examples had thesame level of bleaching agent (about 1%), shows that the ratio of thebleaching efficacy to the fraction of participants who reported toothsensitivity decreases as the ratio of the mean peroxide concentration ofthe multi-phase oral composition smeared onto peroxide test strips tothe standard deviation of the peroxide concentration of the multi-phaseoral composition smeared on peroxide test strips decreases.

Further, combining the observation that: 1) the ratio of the bleachingefficacy to the fraction of participants who reported tooth irritationor reported oral irritation or were observed to have oral irritation was22.923 for Example IV-A and only 5.862 for Example I-B with theobservation that; 2) the ratio of the mean peroxide concentration of themulti-phase oral composition smeared onto peroxide test strips to thestandard deviation of the peroxide concentration of the multi-phase oralcomposition smeared on peroxide test strips was also higher for ExampleIV-A Vs. Example I-B (2.89 Vs. 0.95), even though both examples had thesame level of bleaching agent (about 1%), shows that the ratio of thebleaching efficacy to the fraction of participants who reported toothirritation or reported oral irritation or were observed to have oralirritation decreases as the ratio of the mean peroxide concentration ofthe multi-phase oral composition smeared onto peroxide test strips tothe standard deviation of the peroxide concentration of the multi-phaseoral composition smeared on peroxide test strips decreases.

The above clinical results also show that Example IV-B delivered veryhigh efficacy as measured by the mean decrease in yellowness (−Δb*) of3.204, while having low oral irritation (only 16.7%), low toothsensitivity (only 16.7%), and low oral irritation or tooth sensitivity(only 33.3%).

Comparative Example III

Comparative example III is a tooth whitening strip product with 14% H2O2(from Procter & Gamble, Cincinnati, Ohio, USA). This is an aqueous gelcontaining 14% hydrogen peroxide (H₂O₂)

Bleaching Efficacy of Comparative Example III (Aqueous Gel with 14%H₂O₂)

The bleaching efficacy of a third comparative composition (ComparativeExample III—tooth whitening strip product with 14% H2O2) containing afinal concentration of 14% H₂O₂ in an aqueous gel was measured as a partof five different clinical studies. The target populations were adultparticipants with no previous history of tooth whitening. Participantswere treated with the above comparative aqueous gel with 14% H₂O₂(Comparative Example III) delivered on a strip of polyethylene. All fiveseparate groups (totaling over 100 participants) wore the strip for 30minutes twice daily for 21 days.

Digital images were obtained at Baseline, and the day after the 21^(st)treatment day. The combined results of all five clinical studies on theparticipants who wore the comparative Example III (aqueous gel with 14%H₂O₂) delivered on a strip for 30 minutes twice daily for 21 days areshown in the table below.

Table V shows the results in detail:

Example-IV-B (2.99985% H₂O₂ delivered on a strip and used with anelectromagnetic Comparative Example III radiation source described (14%H₂O₂ aqueous gel herein in the section titled delivered on a strip)“Clinical Protocol”) Treatment time 30 minutes twice daily 60 minutesonce daily Number of treatments days 21 3 Mean change in yellowness−3.09 −3.204 from baseline (Δb*) % of participants who reported 29.616.7 or were observed to have oral irritation that was possibly orprobably related to the product % of participants who reported 38.3 16.7tooth sensitivity that was possibly or probably related to the product %of participants who reported 58.3 33.3 or were observed to have oralirritation or tooth sensitivity that was possibly or probably related tothe product Ratio of bleaching efficacy 10.439 19.186 (−Δb*) to thefraction of participants who reported oral irritation or were observedto have oral irritation that was possibly or probably attributed to thecomposition tested Ratio of bleaching efficacy 8.067 19.186 (−Δb*) tothe fraction of participants who reported tooth sensitivity that waspossibly or probably attributed to the composition tested Ratio ofbleaching efficacy 5.300 9.622 (−Δb*) to the fraction of participantswho reported tooth sensitivity or reported oral irritation or wereobserved to have oral irritation that was possibly or probablyattributed to the composition tested

Comparative Example III (aqueous gel with 14% H₂O₂, delivered on a stripfor 60 minutes) produced a mean change in yellowness of −3.09 whileExample-IV-B (also delivered on a strip, and used with anelectromagnetic radiation source) delivered a mean change in yellownessof −3.204 even though it had approximately 466% lower concentration ofH₂O₂ vs. the aqueous gel (2.99985% H₂O₂ Vs. 14% H₂O₂) used inComparative Example III. These results show the surprisingly highefficacy of Example IV-B especially since it was it was treated for only3 days (once daily) while Comparative Example III was treated for 21days (twice daily).

Furthermore, Comparative Example III delivered a high efficacy (−Δb* of3.09), but also had high oral irritation (29.6%), high tooth sensitivity(38.3%), and high oral irritation or tooth sensitivity (58.3%). Incontrast, Example IV-B also delivered high efficacy (−Δb* of −3.204)while having low oral irritation (only 16.7%), low tooth sensitivity(only 16.7%), and low oral irritation or tooth sensitivity (only 33.3%).These clinical results highlight the surprisingly high efficacy combinedwith the surprisingly low oral irritation and tooth sensitivity ofExample IV-B.

The ratio of bleaching efficacy (−Δb*) to the fraction of participantswho reported oral irritation or were observed to have oral irritationwas 19.186 for Example IV-B and 22.923 for Example IV-A Vs. only 10.439for Comparative Example III. Similarly, the ratio of bleaching efficacy(−Δb*) to the fraction of participants who reported tooth sensitivitywas 19.186 for example IV-B and >100 for Example IV-A Vs. only 8.067 forcomparative Example III. Similarly, the ratio of bleaching efficacy(−Δb*) to the fraction of participants who reported tooth sensitivity orreported oral irritation or were observed to have oral irritation was9.622 for Example IV-B and 22.923 for Example IV-A Vs. only 5.300 forComparative Example III. These data highlight the surprisingly highratio of bleaching efficacy to tooth sensitivity and/or oral irritationdelivered by Examples IV-B and IV-A.

The dimensions and values disclosed herein are not to be understood asbeing strictly limited to the exact numerical values recited. Instead,unless otherwise specified, each such dimension is intended to mean boththe recited value and a functionally equivalent range surrounding thatvalue. For example, a dimension disclosed as “40 mm” is intended to mean“about 40 mm.”

Every document cited herein, including any cross referenced or relatedpatent or application and any patent application or patent to which thisapplication claims priority or benefit thereof, is hereby incorporatedherein by reference in its entirety unless expressly excluded orotherwise limited. The citation of any document is not an admission thatit is prior art with respect to any invention disclosed or claimedherein or that it alone, or in any combination with any other referenceor references, teaches, suggests or discloses any such invention.Further, to the extent that any meaning or definition of a term in thisdocument conflicts with any meaning or definition of the same term in adocument incorporated by reference, the meaning or definition assignedto that term in this document shall govern.

While particular embodiments of the present invention have beenillustrated and described, it would be obvious to those skilled in theart that various other changes and modifications can be made withoutdeparting from the spirit and scope of the invention. It is thereforeintended to cover in the appended claims all such changes andmodifications that are within the scope of this invention.

What is claimed is:
 1. A multi-phase oral composition comprising: a)from about 0.9% to about 60% by weight of the multi-phase oralcomposition of an aqueous phase having a bleaching agent, wherein theamount of the bleaching agent in the multi-phase oral composition isfrom more than 0.5% to about 20%; b) from about 40% to about 99.1% byweight of the multi-phase oral composition of a hydrophobic phase;wherein the multi-phase oral composition has a cone penetrationconsistency value from about 50 to about 400 as measured by ASTMD937-07; and the hydrophobic phase has a melt point from about 30° C. toabout 90° C. as measured by ASTM D127-08.
 2. The multi-phase oralcomposition according to claim 1, wherein the cone penetrationconsistency value of the hydrophobic phase or the multiphase oralcomposition is from about 100 to about 300, as measured by ASTM D937-07.3. The multi-phase oral composition according to claim 2, wherein thecone penetration consistency value of the hydrophobic phase or themultiphase oral composition is from about 100 to about 250, as measuredby ASTM D937-07.
 4. The multi-phase oral composition according to claim1, wherein the drop melting point of the hydrophobic phase is from about40 C to about 80 C, as measured by ASTM D127-08.
 5. The multi-phase oralcomposition according to claim 4, wherein the drop melting point of thehydrophobic phase is from about 50 C to about 80 C, as measured by ASTMD127-08.
 6. The multi-phase oral composition according to claim 1,wherein the two-dimensional density of droplets with a cross-sectionalarea larger than about 10000 square microns measured using the procedurespecified herein is no more than about 20 per square centimeter.
 7. Themulti-phase oral composition according to claim 6, wherein thetwo-dimensional density of droplets with a cross-sectional area largerthan about 10000 square microns measured using the procedure specifiedherein is no more than about 10 per square centimeter.
 8. Themulti-phase oral composition according to claim 1, wherein the standarddeviation of the peroxide intensity of the multi-phase oral compositionsmeared onto peroxide test strips measured using the procedure specifiedherein is no more than about
 50. 9. The multi-phase oral compositionaccording to claim 8, wherein the standard deviation of the peroxideintensity of the multi-phase oral composition smeared onto peroxide teststrips measured using the procedure specified herein is no more thanabout
 25. 10. The multi-phase oral composition according to claim 1,wherein the mean peroxide intensity of the multi-phase oral compositionsmeared onto peroxide test strips measured using the procedure specifiedherein is from about 1 to about
 100. 11. The multi-phase oralcomposition according to claim 1, wherein the mean residual peroxideintensity of the multi-phase oral composition smeared on teeth measuredusing the procedure specified herein is from about 20 to about
 200. 12.The multi-phase oral composition according to claim 11, wherein thebleaching agent in the multi-phase oral composition comprises hydrogenperoxide.
 13. The multi-phase oral composition according to claim 1,wherein the hydrophobic phase comprises at least one of: mineral oilthickened with wax, mineral oil thickened with polyethylene, orpetrolatum.
 14. The multi-phase oral composition according to claim 1,wherein the bleaching efficacy of the multi-phase oral compositioncalculated as −Δb* and measured per the clinical protocol as disclosedherein is at least about 1.5.
 15. The multi-phase oral compositionaccording to claim 1, wherein the ratio of the bleaching efficacy of themulti-phase oral composition calculated as −Δb* and measured per theclinical protocol as disclosed herein to the weight percentage ofbleaching agent present in the overall multi-phase oral composition isat least about 1.5.
 16. The multi-phase oral composition according toclaim 1 comprising a delivery carrier.
 17. The multi-phase oralcomposition according to claim 16 wherein the delivery carrier is astrip.
 18. A method for whitening teeth comprising using multi-phaseoral composition according to claim 16 comprising: a) applying themulti-phase oral composition to the delivery carrier; b) applying thedelivery carrier to at least one tooth surface, such that the deliverycarrier contacts the multi-phase oral care composition against the atleast one tooth surface.
 19. A kit for whitening teeth comprising: a)the multi-phase oral composition of claim 16; and b) an electromagneticradiation source capable of directing electromagnetic radiation with oneor more wavelengths in the range from about 200 nm to about 1700 nmtowards at least one tooth.
 20. The kit for whitening teeth according toclaim 19, wherein the electromagnetic radiation source emitselectromagnetic radiation in the range from about 400 nm to about 500nm, impinging on the outer surface of the delivery carrier in the rangefrom about 175 mW/cm2 to about 225 mW/cm2 measured using the proceduresdescribed herein.